Thorax: first published as 10.1136/thx.40.3.209 on 1 March 1985. Downloaded from Thorax 1985;40: 209-240
Proceedings of the British Thoracic Society
The 1984 winter meeting of the British Thoracic Society was held on 6-7 December at the Kensington Town Hall, London W8
Cavitation in aseptic pulmonary infarction patients have returned to work. Three patients have been lost to follow up and 14 have died, 0.2-12.7 (median 2.25) RJA BUTLAND, AEA JOSEPH, KB SAUNDERS, AG WILSON Ten years after starting treatment, 12 from cardiorespiratory patients with aseptic embolic pulmonary infarcts which failure - caused in eight by progressive muscular cavitated are reported. Six of the 10 patients were female weakness. Thus longevity and quality of survival have been and four male, and their ages ranged from 58 to 79 years. improved, particularly in patients in whom the causative Nine patients had significant underlying cardiac or condition is stable. pulmonary disease (five had chronic airflow obstruction and seven had left ventricular failure), which probably predisposed to cavitation. In only one case did infection Mediastinal imaging in lung cancer (secondary) of a longstanding infarct precipitate cavitation and in the rest cavitation was aseptic, though in three cases R MILROY, L SMITH, A FAICHNEY, D ANDERSON, I STEWART, J significant late (or tertiary) infection of an aseptic cavity McKILLOP, S BANHAM, K DAVIDSON Accurate mediastinal occurred. Thus the view proposed in the preantibiotic era staging is vital for appropriate management of lung cancer that cavitation is the consequence of secondary infection (Spiro SG, Goldstraw P. Thorax 1984;39:401-7). The role may no longer be correct. Cavities were single in eight and of computed tomography (CT) and gallium 67 multiple in two patients, and showed a predilection for scintiscanning however, remains uncertain because these copyright. apical or apicoposterior segments (80%). Strands or bands techniques have not been simultaneously compared with traversing the cavity and a scalloped inner wall were a mediastinal exploration. We report our initial findings in feature. Half showed an air-fluid level at some time, such a study of 40 patients. Gallium scanning sensitivity including all those that developed secondary or tertiary was 64.30/, specificity 80.80/o. The predictive value of infection. At follow up after at least one year five patients positive result was 64.3%7o and of a negative result 80.80/o had persistent cavities (of which two contained an with overall accuracy of 757o. CT scanning sensitivity was http://thorax.bmj.com/ aspergilloma) and in two only a scar remained. Aseptic 61.5%/o and specificity 88.50/.. The predictive value of pulmonary infarction should be considered as a cause of positive result was 72.70o and of a negative result 82.10/o cavitation or of abscess formation, especially in patient with an overall accuracy of 79.50/o. Of 14 cases with with left ventricular failure or chronic airflow obstruction. positive results for mediastinoscopy gallium and CT scanning both gave correct results in five and one of the techniques gave a correct result in a further seven cases. In Survival with term 26 cases with negative mediastinoscopy results, gallium and long respiratory support CT scanning both gave correct results in 19 cases and in EH SAWICKA, L LOH, MA BRANTHWAITE Fifty-one patients only one case were both incorrect. The study suggests that with respiratory failure caused gallium and CT scanning are complementary and if both on September 27, 2021 by guest. Protected primarily by neuromuscular the gallium and the CT scan are negative then it is (29) or skeletal disease (22) have been treated for 0.2-18 reasonable to proceed directly to thoracotomy. If either the years with ventilatory support. Mean age at presentation gallium or the CT scan is positive then we would suggest was 48 years, with cor pulmonale present in 790/o with that mediastinal skeletal deformity but only in 22% with neuromuscular exploration is undertaken. disease. Nine patients were treated initially with intermittent positive pressure ventilation, the remainder Lung cancer in south east Scotland 1981-1984: the with negative pressure ventilation from the outset. Forty- Edinburgh lung cancer group four use negative pressure ventilation and three positive pressure ventilation with a permanent tracheostomy during S CAPEWELL for the Edinburgh Lung Cancer sleep at home. Four require occasional or regular three day Group Scotland has one of the highest lung cancer rates in periods of hospital admission for intensive negative the world, over 120/105 in men. The Edinburgh Lung pressure ventilation. Fourteen patients have a Cancer Group, formed in 1980, comprises physicians, tracheostomy, used as a means of providing ventilatory surgeons, radiotherapists, oncologists, pathologists, and support in only three. Breathlessness has been lessened in radiologists. In the three complete years 1981-3 we have all patients, hospital admission has been infrequent, cor recorded data on 2057 patients seen in hospital practice, pulmonale has resolved, and diurnal arterial blood gas representing at least 850/o of cases in our estimated tensions have improved in 40 or 44 patients. At least 26 population of 950 000. The cell type was know in 1660 209 Thorax: first published as 10.1136/thx.40.3.209 on 1 March 1985. Downloaded from 210 Proceedings ofthe British Thoracic Society
(81%o) and included 50%o squamous and 23% small cell given tetracycline. In the succeeding three months complete carcinomes, 12% adenocarcinomas, and 12% large cell responses were similar (830%o and 73% respectively). Side carcinomas. There were 88 patients aged under 50, with effects were uncommon with both treatments; pleural pain significantly more adenocarcinoma compared with the however, occured in 23% of patients given tetracycline older patients (18%o v 10%, p<0.01) and less squamous despite prior analgesia. Nausea and vomiting occurred in carcinoma (31%1o v 41%, p<0.05); 36% of patients were 15% and rigors in 6% of patients given bleomycin. aged over 70. There were 547 cases of known cell type diagnosed in 1981, of whom only 71 (13%7o) were alive two years later. Survival was best for adenocarcinoma (25%, all Postal survey' of medical bronchoscopies in the United survivors having been treated surgically). This was Kingdom: Drugs and safety precautions significantly better than the 14%o with squamous carcinoma and the 7% with small cell carcinoma (p<0.05). Forty- FG SIMPSON, AG ARNOLD, A PURVIS, MF MUERS, NJ COOKE A Four of the survivors were treated surgically, nine by postal survey of British bronchoscopic practice revealed radiotherapy and six with chemotherapy. More than half mortality and morbidity rates which, though low, were the patients presenting in 1981 were treated actively (379) higher than previous estimates (Arnold et al. Thorax yet only 59 (16%) were alive after two years, some with 1984;39:219). Published recommendations regarding the residual disease. These data suggest that there is a case for use of sedatives and of local anaesthetics and safety improving the selection of patients before active treatment. precautions for fibreoptic bronchoscopy vary considerably. We present further data from the 1983 questionnaire concerning these factors. Of 199 physicians performing Oral salbutamol and pholcodine for cough fibreoptic bronchoscopy under local anaesthesia, 186 used sedative drugs. One hundred and three physicians used a PJ REES, N BELCHER We have measured cough threshold by single sedative (80% choosing an opiate), 68 used two using doubling doses of citric acid as three breaths from a drugs, and 15 used three or more drugs in combination. breath actuated dosimeter in 11 non-asthmatic subjects. On Eighteen (9%o) physicians reported using drug combinations four separate days the cough threshold was measured, and which could be considered illogical or potentially then repeated two hours after they had taken orally 4 mg hazardous. The mean dose of lignocaine used was 342 salbutamol, 10 mg pholcodine, 4 mg salbutamol, and 10 mg (range 100-1160) mg, most operators using more than the pholcodine or placebo in a double blind randomised maximum recommended dose of 300 mg. Eighty-seven per fashion. Pholcodine alone and in combination with cent of operators had facilities for immediate endotracheal copyright. salbutamol produced significant increases in cough intubation, but only 68% had a defibrillator to hand, 41% threshold. No significant change was seen after oral a rigid bronchoscope, and 27% a balloon catheter. Routine salbutamol alone or placebo. The effect of pholcodine was supplemental oxygen was given by 18%7o of respondants; not increased by combination with salbutamol. These 9.50o never gave oxygen. These results show great results confirm the effectiveness of pholcodine as a variability in bronchoscopic practice, especially with regard suppressant of induced coughs and show that oral to use of drugs, and generally poor compliance with http://thorax.bmj.com/ salbutamol is ineffective alone or as an addition to recommended safety precautions, though it may well be pholcodine in suppressing coughs in non-asthmatic that it is the recommendations which require modification. subjects. Fibreoptic bronchoscopy in the investigation of community Comparison of intrapleural bleomycin and tetracycline in acquired pnemonia the treatment of malignant pleural effusion NJ ALI, BDW HARRISON, PF JENKINS Eighteen patients with a CE JOHNSON, PGD CURZON, Sixty patients with provisional diagnosis of pneumonia underwent histologically proved malignant pleural effusion (two with bronchoscopy under local anaesthesia as part of their initial on September 27, 2021 by guest. Protected bilateral effusion) were randomly allocated to recieve investigation. Two subsequently proved to have pulmonary intrapleural instillation of either bleomycin sulphate emboli. A positive microbiological diagnosis was obtained (Img/kg) or tetracycline hydrochloride (1 g) following from bronchial aspirate in 11 of 16 patients with intercostal tube drainage of the effusion. The method of community acquired pneumonia (Streptococcus randomisation ensured equal distribution of the various pneumoniae (5), haemolytic streptococcus (2), S malignancies to the two treatment groups. Patients' enterococcus (1), H influenzae (2), Mycoplasma progress was assessed monthly after treatment for up to six pneumoniae (1)). With conventional methods of sputum months with chest radiographs, spirometry, and where and blood cultures, including serology and use of appropriate pulmonary ultrasound. A complete response pneumococcal antigen, a correct diganosis would have been represented no reaccumulation of pleural fluid. A partial achieved in only four of these 16 patients. In nine of the 1 1, response represented reaccumulation not requiring Gram staining of bronchial aspirate demonstrated the intervention, while no response required repeat pleural correct organism confirmed by culture. Pneumococcal aspiration. Reintervention was required in only seven antigen (Pn Ag) was detected in bronchial aspirate from patients (1 %), two treated with bleomycin and five treated two patients with non-pneumococcal pneumonia and one with tetracycline (this difference is not significant). Over with pulmonary embolus. In one case Pn Ag was not the first three months a complete response was achieved in detected despite culture of pneumococcus from bronchial 87% of patients given bleomycin and in 5601-of patients aspirate. These results suggest that the Pn Ag may give both Thorax: first published as 10.1136/thx.40.3.209 on 1 March 1985. Downloaded from Proceedings of the British Thoracic Society 211 false negative and false positive results. On direct those selected. The prevalance of some work related questioning three patients said that they had found the symptoms differed significantly between the two buildings. procedure unpleasant, the remaining 15 describing only An environmental assessment of the offices was done on minimal discomfort. We conclude that fibreoptic three different occassions. Globe temperature, dry bulb bronchoscopy is a reliable, well tolerated procedure in the temperature, relative humidity, air velocity, positive and investigations of a condition that still carries high negative ions, and formaldehyde measurements were all mortality. made. None of these factors differed between the buildings, suggesting that building sickness is caused by other factors. Prednisolone in the treatment of airflow obstruction in adult patients with cystic fibrosis Effect of corticosteroids on neutrophil function in bronchial asthma RJ STEAD, CFA PANTIN, ME HODSON, JC BATTEN Thirteen adult patients with cystic fibrosis and severe airflow W GIN, AB KAY We have previously reported that peripheral obstruction (median FEV1 27.50/o predicted, range 1649), blood monocytes from asthmatics were activated, as shown who had been clinically stable for three months, received by enhanced expression of membrane receptors, and that placebo prednisolone tablets followed by prednisolone 30 this was reversed by corticosteroids. Since there is a paucity mg/day (20 mg/day if body weight < 50 kg) for consecutive of information on the role of neutrophils in ongoing three week periods. Other therapy remained unchanged, asthma, we have examined the effects of corticosteroids on except for antibiotics as clinically required. Patients were neutrophil activation by assessing (a) the expression of assessed when treatment was changed and one month after membrane complement (C) receptors and (b) the capacity the study. They also completed diary cards, including thrice of these cells to respond in directional cell locomotion daily peak flow recordings. The group showed no (chemotaxis). Compared with 17 healthy controls, significant changes in any of the following while taking in neutrophil C receptor expression was significanlty increased placebo or prednisolone or the follow-up period: six (p<0.05) in 31 asthmatics not receiving prednisolone, and minute walk, PEF, FEV1, FVC, dyspnoea (MRC grading). significantly decreased (p<0.001) when compared with The diary cards showed no change in PEFR, feeling of levels in 19 general well being, breathlessness, sputum volume, or asthmatics receiving prednisolone. In a further presence of wheeze. No patient had a > 10% improvement five patients neutrophil locomotion in vitro in response to a in or FVC in known chemoattractant (casein) was enhanced when PEFR, FEVI, measured the clinic following copyright. prednisolone compared with the best achieved with placebo compared with that in controls, but significantly decreased or at follow-up, but one patient had a >10% improvement after a seven-day course of oral prednisolone (30 mg/day). in home PEFR. Two patients developed pneumothoraces These studies indicate that there is altered neutrophil while taking prednisolone; one required pleurodesis and function in chronic asthma and that this reversible by oral withdrawal from the study. Three patients developed mild corticosteroids.
glycosuria. This small study does not suggest that http://thorax.bmj.com/ prednisolone improves severe but stable airflow limitation in cystic fibrosis. Effect of theophylline in plasma on cyclic AMP metabolism PK GREWAL, JS MANN, ST HOLGATE It is widely quoted that Building sickness a comparison of work related health the effect of theophylline in asthma occurs through problems and environmental measurements in two office inhibition of cyclic AMP phosphodiesterase to increase buildings with different ventilation systems cellular levels of cyclic AMP. It has been suggested, however, that therapeutic plasma theophylline levels are AS ROBERTSON, PS BURGE, M FINNEGAN, CAC PICKERING, A too low to achieve this effectively. In asthmatic subjects we
HEDGE, J SIMMS, F GILL, G. DALTON A cross sectional survey have investigated the effect of incubating plasma obtained on September 27, 2021 by guest. Protected was carried out in two buildings with similar office worker before and at 0.5, 1.0, and 2.0 hours after oral theophylline populations but different ventilation systems, one being (T) 375 mg, on leucocyte and dispersed human lung cell fully air conditioned with humidification and the other (DHLC) levels of cyclic AMP in the absence and presence naturally ventilated. A stratified, randomly selected sample of isoprenaline I 100,uM. Mean (SD) plasma theophylline of workers was seen in each building. Two hundred and reached a maximum 1.5 hours after administration of 11.20 forty-one workers in all were seen, representing 79% of (0.8) pg/ml and was accompanied by increases of 26.2% (11.8%) and 58.4% (26.3%) in FEVY and sGaw respectively Naturally without significantly affecting plasma cyclic AMP levels. Humidified Ventilated P value Mean basal (B) leucycyte cyclic AMP was 4.7 (1.1) (%) (%) (X2) pmol/106 cells, which increased after incubation with post theophylline plasma taken at all time points in all subjects. Lethargy 36.4 13.4 < 0.001 Headache 31.0 15.2 0.004 With plasma theophylline at 1.5 hours (11.2 ,ug/ml) Itching of eyes 21.9 7.1 0.001 leucocyte cyclic AMP increased to 5.7 (1.5) (T), with Runny nose 27.6 5.4 <0.001 isoprenaline alone (I) to 7.1 (1.7), and with theophylline Stuffy nose, dry throat 34.9 9 <0.001 Breathlessness 3.2 1.8 0.2 plus isoprenaline (T + I) to 10.4 (1.7) pmol/106 cells. Wheeze 8.6 4.5 0.5 Corresponding values for DHLC were B 1.4 (0.1), T 1.7 (0.3), I 2.8 (0.8), and T + I 4.6 (0.7) pmol/106 cells. At all Thorax: first published as 10.1136/thx.40.3.209 on 1 March 1985. Downloaded from 212 Proceedings of the British Thoracic Society plasma time points the interaction between theophylline the maximal effective dose of salbutamol in some subjects, and isoprenaline was not significantly different from but that aminophylline, administered acutely, has little additive and therefore does not support a major inhibitory further effect. effect of theophylline on phosphodiesterase. Plasma sodium cromoglycate levels with nebuliser and Enhancement of the peripheral adrenergic response by metered dose aerosol in patients with exercise induced hydrocortisone asthma RI GOVE, PS BURGE Inhibition of the intradermal histamine WM TULLETT, KM TAN, MG NEALE, RT WALL, KR PATEL As induced weal and flare by salbutamol and noradrenaline sodium cromoglycate is poorly absorbed from the was measured in 23 patients with chronic airflow gastrointestinal tract, the drug concentration appearing in obstruction before and after the administration of plasma reflects the drug absorbed from the lungs. With a hydrocortisone. Three coded injections of 50 1 were given sensitive radioimmunoassay, plasma levels of sodium intradermally into the flexor surfaces of both forearms. All cromoglycate were measured in 11 patients (aged 19-51) injections contained 50 pg of histamine in phosphate years) with exercise induced asthma. We compared the buffered saline. In addition one contained 100 pg of effect of 2, 10, and 20 mg aerosol sodium cromoglycate salbutamol and another 3 pg of noradrenaline. The with a placebo in a double blind study. The effect of resulting weal volumes were measured after 12 minutes and sodium cromoglycate nebuliser solution was also studied the mean of the volumes of both forearms recorded. The (lOg/l - estimated dose 12 mg). The patients were measurements were repeated six hours after the exercised on a treadmill for 6-8 minutes. The peak plasma administration of 1 g hydrocortisone intravenously. Both levels (mean (SEM)) of sodium cromoglycate with nebuliser noradrenaline and salbutamol significantly inhibited the solution and 2, 10, and 20 mg aerosol were 14.1 (1.6), 1.3 histamine weal volume (noradrenaline v salbutamol: (0.2), 3.4 (0.9), and 6.3 (1.1) ng/ml respectively. The p 0.01). Intravenous hydrocortisone did not significantly plasma levels with nebuliser solution were significantly alter the mean histamine alone weal volume (mean (SD), p1: higher than with aerosol doses (p<0.00l). There was a dose prehydrocortisone 139.3 (67); posthydrocortisone 119.0 related increase in plasma levels with aerosol formulations. (80)) but significantly reduced both the salbutamol and The mean percentage protection after nebuliser solution noradrenaline weals (mean (SD), p1: salbutamol and 2, 10, and 20 mg sodium cromoglycate aerosol was 65 prehydrocortisone 87.5 (48.5); salbutamol (8), 40 (11), 59 (7), and 67 (6) respectively. Sodium copyright. posthydrocortisone 69.2 (33.6) (p<0.05); noradrenaline cromoglycate inhibited exercise asthma at all doses used prehydrocortisone 58.4 (30.7), noradrenaline and the protection increased from 2 to 20 mg. The posthydrocortisone 36.1 (16.1) (p<0.01)). The results show protective effect of 20 mg sodium cromoglycate aerosol was that a and ,B adrenergic responses are increased comparable to that of 12 mg nebulised sodium significantly, but a similar non significant order of change cromoglycate. There was no correlation between protection was seen for histamine. It is possible that hydrocortisone afforded by sodium cromoglycate and the plasma levels of http://thorax.bmj.com/ was acting as an anti-inflammatory agent, independent of sodium cromoglycate. adrenergic receptors, or that there is potentiation of a and ,B adrenergic receptors in the skin. The effect of long term high dose ipratropium bromide on lung mucociliary clearance Can you better a beta stimulant? RG TAYLOR, D PAVIA, JE AGNEW, M-T LOPEZ-VIDRIERO, SP J CHAIEB, N BELCHER, PJ REES, TJH CLARK Eleven patients NEWMAN, T LENNARD-JONES, SW CLARKE We have compared in a double blind crossover study the effect on lung with persistent airflow obstruction with their current on September 27, 2021 by guest. Protected bronchodilator therapy have been studied. They were given mucociliary clearance of placebo and high dose salbutamol by inhalation in doubling doses until two ipratropium bromide (200 yg thrice daily) given by metered consecutive doses had both failed to increase FEV1 by 1O%. dose inhaler for one month. We studied eight subjects with All subjects still had a FEVy of 85% or less of their chronic obstructive airways disease (median (range) FEVy predicted values. They were then given 160 Hg of 46% (24-70%) predicted) and seven with asthma (FEVy ipratropium bromide by metered dose inhaler, and three of 70% (29-91 %1) predicted). Seven subjects produced sputum the 11 increased their FEVI over the next 60 minutes by regularly, two of whom had asthma. Subjects maintained more than 10%. All subjects still had an FEV1 of less than their usual treatment with theophylline, oral and inhaled/32 90% predicted. They were all then given intravenous agonists and corticosteroids. Clearance of lung secretions aminophylline at a dose of 5.6 mg per kg, achieving blood was measured with an objective, non-invasive radioaerosol levels of 8-15 mg/l 30 minutes later. No subject showed a technique. The number of coughs and the wet weight, 10% increase in FEVy after aminophylline. Similar results radioactive content and mean apparent viscosity of sputum were seen with FVC values, but specific conductance produced during the six hour observation period were increased by at least 10% in seven of 11 subjects after recorded. Comparison with placebo showed no significant ipratropium bromide, and by a further 10% in four of 11 changes in penetration index or in alveolar deposition of with aminophylline. We conclude that ipratropium inhaled particles, nor significant alteration in uncorrected bromide can produce useful bronchodilatation on top of or cough corrected tracheobronchial clearance (p>0.05). Thorax: first published as 10.1136/thx.40.3.209 on 1 March 1985. Downloaded from Proceedings of the British Thoracic Society 213 Similar results were obtained when the subjects were synchronisation, but decreases patients' augmentation of divided into sputum producers and non-producers. The wet the mechanically induced tidal volume, so allowing the weight of sputum produced, its radioactive content and its Pco2 to rise; The pneumosuit offers advantages over the viscosity were similar with ipratropium and placebo. These Tunnicliffe jacket and cuirass because it distributes results show that high dose inhaled treatment with the pressure over a maximal area of unimpeded synthetic anticholinergic bronchodilator ipratropium thoracoabdominal wall. bromide is not associated with any modification of the clearance of secretions from the lungs. Patterns of breathing during weaning from mechanical ventilation after thoracic surgery Inspiration phased oxygen delivery DL MAXWELL, D ROYSTON, JMB HUGHES Thirteen patients RJD WINTER, RID GEORGE, JC MOORE-GILLON, DM GEDDES A were monitored in the first 24 hours after coronary artery device that produces inspiration phased oxygen delivery bypass graft or valve replacement with respiratory (IPOD) by sensing pressure changes in a standard nasal inductance plethysmography (RIP) for the first 45 minutes cannula was compared with conventional continuous of spontaneous breathing during weaning from mechanical oxygen flow in 20 patients with various severe lung diseases ventilation. Calibration of RIP was carried out immediately (16 chronic bronchitis, two pulmonary fibrosis, and two following discontinuation of mechanical ventilation. Eight cystic fibrosis). When clinically stable all had a PaO2 of less patients were monitored one week later on the ward. The than 60 mm Hg (means 46, range 37-60). Oxygen was given mean (SD) ventilatory values for 10 minute periods before through standard nasal cannulae both intermittently (via and after extubation are displayed in the table. There were IPOD) and continuously at flow rates of 2, 4, and 6 I/min. no significant changes in breathing pattern before and after Changes in Pao2 and Paco2 were measured extubation, in contrast to a previous study on a transcutaneously. In six patients activation characteristics heterogeneous group of postoperative patients (Tobin et and gas flow were studied by interposing a al., ARRD 1984;129:A106). There were significant pneumotachograph in the oxygen line between the device increases in VE (25%,p=0.01) and T1/Ttot (15%,p=0.01) and the nasal prongs while simultaneous recordings of one week later in the eight patients monitored at this time. respiratory movements were made with an inductance The rib cage contribution to ventilation (RC) during plethysmograph. Mean Pao2 increased to 63.2, 79.1, and weaning from mechanical ventilation was no different from 97.4 mm Hg at 2, 4, and 6 I/min with continuous flow, not normal values in the same position, and in eight patients it copyright. significantly different from 68.0, 82.3, and 89.2 mm Hg did not change one week postoperatively despite the with IPOD. To produce the increments in Pao2 seen with 2, thoracic trauma at operation and the effects of anaesthetic 4, and 6 I/min continuous flow, savings in oxygen used of agents. 38%, 430!7, and 44% respectively were achieved with
IPOD. In all patients the negative pressures produced by VE VT Breaths! Tl/ VT/TI RC PaC02 http://thorax.bmj.com/ quiet nose and mouth breathing were sufficient to actuate (l/min) ( min Ttot (l/min) (mm Hg) the device. Delivery of oxygen only during inspiration Before 5.7 0.39 15 0.32 18.1 0.4 46.2 produces worthwhile savings in the volume of gas used and (2.1) (0.16) (4.4) (0.07) (6.7) (0.2) (6.1) will reduce the expense and inconvenience of long term After 6.1 0.38 16.4 0.33 18.2 0.4 45.8 oxygen therapy. (2.0) (0.1) (4.3) (0.06) (4.8) (0.2) (6.5)
Efficiency of negative pressure ventilatory equipment The effects of oral high frequency oscillations (OHFO) on steady state exercise in chronic lung disease
AK SIMONDS, MA BRANTHWAITE Negative pressure on September 27, 2021 by guest. Protected ventilation during sleep can reverse chronic hypercapnia RJD GEORGE, RS HOWARD, A STEARN, DM GEDDES Patients and hypoxaemia and so alter the natural history of walk further in six minutes and recover more quickly when respiratory insufficiency caused by restrictive chest wall their breathing is assisted by OHFO (Thorax 1984;39:717). disorders. The relative efficiency of the cuirass, Tunnicliffe The mechanism is not known. Eight patients (six with jacket, and pneumosuit was investigated by monitoring chronic airflow obstruction, two with cryptogenic fibrosing oxygen saturation, transcutaneous Pco2, oronasal airflow, alveolitis) exercised on a bicycle ergometer at 50% maximum chest wall movement, and EEG/EOG during sleep. Three work load to exhaustion. Results of control tests were problems were identified. A tendency to upper airway compared, in random order, with results with OHFO obstruction may be potentiated by negative pressure delivered by compressor at 25 Hz (Devilbiss) and a ventilation and a reduction in obstructive episodes was loudspeaker at the patient's preferred frequency (12-28 Hz). obtained with protriptyline. Desynchronisation between Minute ventilation (VE) was measured by inductance spontaneous respiratory effort and the applied cycle plethysmography and breathlessness by visual analogue generally occurred during REM sleep and was reduced by score. During the control tests exercise was limited by oxygen therapy. Oxygen therapy, however, often resulted breathlessness in all subjects. With OHFO patients cycled in carbon dioxide retention even though ventilation was longer (Devilbiss 166% control, range 113-235%, p<0.001; supported mechanically. We hypothesise that oxygen loudspeaker 186% control, range 91-324/o p<0.05) and reduces hypoxic ventilatory drive, thereby improving were less breathless. Overall VE was lower with OHFO Thorax: first published as 10.1136/thx.40.3.209 on 1 March 1985. Downloaded from 214 Proceedings ofthe British Thoracic Society (p<0.05). At steady state (minute 6) and at the break point indicate that exercise improves ventilation-perfusion of the control run, VE with the Devilbiss was 83% control relationships in patients with unilateral diaphragmatic (p<0.01 and <0.05 respectively). This was due mainly to a paralysis. mean fall in respiratory rate from 35 to 29 at minute 6 (p<0.01) and from 40 to 32 at the break point (p<0.01). We conclude that improved exercise tolerance and reduction in Staining characteristics of human pulmonary mast cells breathlessness may be attributable to a fall in VE, at least in part. RM AGIUS, D JONES, ST HOLGATE Mucosal and connective tissue mast cells of rats may be differentiated by the effect of fixatives and sequential staining of their granule Assessment of bullous lung disease glycosaminoglycan with alcian blue (AB) and safranin 0 (SO). With the use of labelled mouse monoclonal IgG E MDL MORGAN, CM BUSST, DM DENISON, BS STRICKLAND Fifty chain specific antihuman IgE, mast cells characterised by patients believed to have localised bullous emphysema were their high density of cell bound IgE were identified in referred for regional lung function studies to assess their human tissue sections of airway mucosa, submucosa, suitability for surgery. They were subjected to routine alveolar walls, and pleura as well as bronchoalveolar lavage pulmonary function tests, blood gas estimates, (n = 11, range of differential mast cell counts 0-0.50o). We endobronchial studies of soluble gas exchange, and CT scans investigated whether subpopulations of mast cells could be at TLC and RV. On the basis of the CT scans they were differentiated histochemically using AB/SO staining after divided into two groups: 23 patients with well defined fixation in Carnoy's or formalin based fixatives in human surgically accessible bullae and the remainder with lung sections, dispersed lung preparations, bronchoalveolar generalised disease. There were no demonstrable differences lavage fluid, skin, tonsil; dog mastocytoma; and rat skin, between the two groups in pulmonary function or blood gut, peritoneum, and bone marrow culture. In all human gases. The endobronchial tests of regional lung function lung preparations mast cells stained with AB, as did those identified bullae only when they were ventilated, but in tonsil and in rat bone marrow culture and gut even under otherwise reflected the quality of the non-bullous lung. The conditions of fixation in which significant SO staining was volumes of the bullae were measured in inspiration and present in human skin. In contrast, mast cells in dog expiration. The majority of bullae (82%/) did not ventilate mastocytoma and in rat skin and peritoneum stained appreciably (RV/TLC bulla > 80%) and none ventilated predominantly with SO. Thus it was not possible preferentially. Surgery was recommended in all of this group histochemically to differentiate subpopulations of mast copyright. but only 12 were referred for operation. All those who cells within human lung, although differences were noted at underwent surgery survived, with improvement in pulmonary other sites. function, though many had preoperative lung function that would normally be considered too poor (67% had FEV1
to epithelial membrane antigen (EMA), to cytokeratin stapler was used for bronchial closure during http://thorax.bmj.com/ (CAM 5.2), and to carcinoembryonic antigen (CEA) have pneumonectomy in 71 patients from January 1979 to been used to stain fixed tissue sections of 26 autopsy-proven February 1982, (group I). Since March 1982 the new hinged (or necropsy-proven) pleural mesotheliomas, to see whether jaw stapler (Premium TA-55 has been used in 59 patients their demonstration would be of potential value. There (group II). The incidence of bronchopleural fistula was have been conflicting reports about whether mesotheliomas 4.2% in group I and 15.2% in group II (p>0.O5). The two are CEA negative or not, but when a monoclonal anti-CEA staplers were tested in the laboratory with an unfixed with no NCA (CEX) cross-reactivity was used all were cadaveric right main bronchial preparation and 4.8 mm negative. Twenty-five of 26 were positive with CAM 5.2, staples. The stapled segments of the bronchus were then and 23/26 were positive for EMA. The cytokeratin stains resected and radiographed. With the Premium TA-55 were more intense and widely distributed than those for closure of staples was incomplete near the hinge, whereas on September 27, 2021 by guest. Protected EMA. Generally, few spindle shaped cells were positive and with the old style TA-55 staples were uniformly and sarcomatoid areas were largely negative. Both CAM 5.2 completely closed, achieving the final B-shape. We and anti-EMA picked out epithelial foci in what appeared conclude that the Premium TA stapler has an inbuilt design to be purely sarcomatoid areas. These results confirm the weakness and should be modified before future use in value of CEA in excluding mesothelioma. The other stains major pulmonary resections. may demonstrate epithelial tumour cells in what appears to be sarcomatoid foci, and in "ghost" cells in necrotic tumours. Neither marker is specific for malignancy. Both Leukotrienes In nal hypersensitivity and polyposis CAM 5.2 and anti-EMA stain benign mesothelium and bronchial epithelium. EMA is also present in normal RJ SHAW, A DRAKE-LEE, P FITZHARRIS, 0 CROMWELL, AB alveolar cells. KAY Potential mediators of nasal allergy include the arachidonic acid derived leukotrienes (LT). These lipid mediators cause smooth muscle contraction, stimulation of Atypical carcinold tumours of the lung: histological mucus secretion, alteration of vascular permeability and features and prognosis after surgery tone (LTC4, LTD4), and activation of inflammatory leucocytes (LTB4). In this study, the observation that LTC4 DJL MALONEY, A MORRITr, PR WALBAUM, D LAMB Though and LTB4 were released into nasal secretions after allergen Thorax: first published as 10.1136/thx.40.3.209 on 1 March 1985. Downloaded from 216 Proceedings of the British Thoracic Society challenge (Thorax 1984;39:699) has been extended to exposure. Varying the interval between the steps produced include examination of the intercellular oedema fluid of no significant differences in test results. Changing the unchallenged nasal polyps. With the use of both specific pattern of breathing had no effect on airway responsiveness radioimmunoassay and RP-HPLC, the intercellular provided that the patient maintained a constant minute oedema fluid of nasal polyps removed surgically from four ventilation. This implies that it is unnecesary to monitor the patients was shown to have immunoreactive LTC4 peaks on rate and depth of respiration continuously in order to reverse phase high pressure liquid chromatography achieve a given minute ventilation, making the technique corresponding to LTC4, LTD4, and LTE4. This study simpler. In addition, a "CO2 requirement graph" has been suggests that not only may leukotrienes be important constructed at different levels of ventilation. This allows mediators of acute allergic reactions in the nose but that the inspired CO2 concentration to be preset, eliminating the they may be present in nasal polyps and thus contribute to need for continuous monitoring with a capnograph to keep the symptoms of this condition. the subject isocapnic during hyperventilation. This makes the procedure easier and reduces the cost of the equipment. A comparison of three methods of assessing nasal airway response to topical histamine Does baseline airway calibre affect the response to inhaled histamine in asthmatics? DM SHELTON, LJF YOULTEN, TB CHAN, NM EISER Three methods of assessing nasal airway response - namely, EH WALTERS, P EBDEN, J BANKS, AT FENNERTY, C peak nasal inspiratory flow (PNIF), nasal airway resistance BEVAN Inhalation histamine log dose-response curves by posterior rhinomanometry (PR) and passive anterior were constructed on two separate occasions, several weeks rhinomanometry (AR) - were compared, in duplicate, in apart, in a group of 13 mild to moderate asthmatic patients. six normal subjects (three atopic). Following 10 baseline Changes in airway calibre were monitored in terms of measurements, 0.13 ml of histamine acid phosphate in specific airway conductance (sGaw). Doses of histamine saline was sprayed into each nostril at increasing consisted of 10 standardised tidal breaths taken from a concentrations, from 0.5 mg/ml to 40 mg/ml. Ninety Wright nebuliser, and were separated by three minute seconds after each dose four measurements of nasal intervals. A linear regression was computed for all points patency were made. The cumulative dose of histamine representing a 1507 or greater fall in sGaw. From this were which either halved PNIF or doubled nasal resistance obtained the log concentration corresponding to a fall in (measured by PR or AR) was taken as the provocation dose sGaw of 200o (log D20) and the slope. There was a strong copyright. (PD-histamine). Mean coefficients of variation of baseline correlation between all baseline sGaw values and the slopes measurements were; PNIF 9.8% (range 4-39%), PR 26% of the subsequent log dose-response curves (r = 0.80, (8-53%), and AR 6%o (1.4-14%). PD-Histamine values p<0.001). There was also a strong correlation between showed no significant difference between any of the individual changes in baseline sGaw between study days and changes in slope (r = 0.75, p<0.01). Overall, there were methods. Mean (SD) PD-histamine was significantly lower http://thorax.bmj.com/ in the atopic subjects (1.15 mg (0.92)) than in the non- weaker, but significant, correlations also between baseline atopic subjects (2.12 (1.35)), there was however, a wide sGaw and log D20, and between log D20 and slope. These intrasubject variability in PD-histamine values. The AR relationships however, disappeared when corresponding method, which measured resistance in each nostril, changes between study days were analysed. This suggests demonstrated up to 10 fold differences in PD-histamine that although the "reactivity" of the airways (slope) is values between nostrils after simultaneous challenge. While closely dependent on baseline calibre per se, the the sensitivity of all three method4 of measurement of nasal "sensitivity" (log D20) is not, although like baseline this patency was similar, the reproducibility was highest for AR does reflect the underlying state of the airways. measurements. on September 27, 2021 by guest. Protected Refractory period following histamine provoked Cold air test: a simplified standard method for airway bronchospasm in asthmatic subjects reactivity MJ CONNOLLY, DJ HENDRICK Although there is some BK ASSOUFI, MB DALLY, AJ NEWMAN TAYLOR, DM DENISON We debate, most investigators have failed to demonstrate a have developed a simple and standardised test based on refractory period following histamine provoked cold air inhalation to measure the level of bronchial bronchospasm. This suggests that the mechanism of reactivity quantitatively. This consisted of stepwise bronchospasm provoked by histamine is fundamentally increases in ventilation of dry subfreezing air at 10%, 20%, different from that provoked by exercise or cold air 40%7o, and 6007. of predicted indirect maximum breathing hyperventilation. We have assessed the effect of repeated capacity (IMBC). For each step the inhalation time was histamine challenge in ten asthmatic subjects, aged 18-50 three minutes. The optimal time between the steps was five years, using the Johns Hopkins dosimeter technique. minutes. Exposure ceased either when a fall in forced Bronchial reactivity was expressed as the "provoking dose" expiratory volume in one second (FEVI) of more than 20% of histamine needed to produce a 2007 fall in FEV, (PD20). of baseline occurred or when there was no response after In our hands PD20 is reproducible within one log dose when breathing cold air at 60% predicted IMBC. The effect of measured on separate days. Challenges were repeated 45-60 cold air was almost fully developed after three minutes' minutes apart, provided that the subject's FEVy had Thorax: first published as 10.1136/thx.40.3.209 on 1 March 1985. Downloaded from Proceedings of the British Thoracic Society 217 spontaneously returned to within 90%o of baseline. In eight Asthmatic subjects are hyperresponsive to inhaled but not subjects bronchial reactivity diminished significantly and intravenous atropine the overall geometric mean PD20 rose from 3.20 to 9.38 units (one unit = a 10 pl inhalation of histamine 1 mg/ml). MK GILLETT, PD SNASHALL Using methods previously Six of the eight subjects who showed diminished reactivity described (Clin Sci 1984;66:665), we have measured airway were challenged a third time and five showed a further responsiveness to methacholine (as defined by PD35) in six decrease in reactivity. In two subjects bronchial reactivity normal and six asthmatic subjects. On separate occasions to histamine remained stable over three successive the methacholine was blocked by premedication with challenges. These results support the existence of a atropine given by aerosol (1.28, 0.64, 0.32, or 0.16 mg) or refractory period following histamine provoked intravenously (0.5 or 1.0 mg). The blocking effect of bronchospasm in a majority of asthmatic subjects. atropine was quantified by the amount of rightward shift in the methacholine dose-response curve, as measured by the dose ratio (DR), where DR = PD35 after atropine/control PD35. We found that intravenous atropine was equally Effect of intramuscular killed influenza virus on airway effective in blocking methacholine in normal and asthmatic responsiveness and clinical state in patients with asthma subjects. Some asthmatics, however, were much more sensitive to inhaled atropine than normal subjects. DR for J BANKS, C BEVAN, A FENNERTY, P EBDEN, EH WALTERS, AP 1.0 mg intravenous atropine = 3.1-33.5 asthmatics, SMITH When nineteen stable asthmatic patients were given 8.9-46.4 normals; DR for 1.28 mg inhaled killed influenza virus intramuscularly, an increase in airway atropine= 13.1-296.4 asthmatics, 10.3-39.4 normals. By sensitivity to histamine was demonstrated 48 hours later in both routes log DR was a function of log atropine dose. those who developed a fourfold or greater rise in The subjects most sensitive to inhaled methacholine were haemagglutination antibodies. This was not associated with most sensitive to inhaled atropine. In conclusion, we believe a deterioration in asthma symptoms or peak expiratory that the hyperresponsiveness of some asthmatics to inhaled flow rate or an increase in bronchodilator requirements in atropine is due to a higher concentration of atropine at its the group of patients studied. Similar changes in airway receptor on bronchial smooth muscle, due to either responsiveness in patients with more severe, less stable increased permeability or increased deposition. The same asthma might, however, lead to acute exacerbation of their factors would appear to contribute to sensitivity to condition. This should be borne in mind when offering methacholine. vaccination to such patients. copyright. Histamine and epithelial permeability in normal and asthmatic subjects Bronchial histamine reactivity in diabetic subjects with and D SHELTON, PJ REES, N EISER, TB CHAN, TJH CLARK Inhalation
without autonomic neuropathy http://thorax.bmj.com/ of histamine is known to increase the permeability of the RE HEATON, RJC GUY, PJ WATKINS, JF COSTELLO We have respiratory epithelium to 99mTc DTPA. We have examined previously reported diminished bronchial reactivity to cold the effects of inhalation of histamine on epithelial air in diabetic subjects with automatic neuropathy. We now permeability in nine asthmatic and six non-asthmatic subjects. subjects. Baseline DTPA clearance was similar in the two report the reactivity to inhaled histamine in these groups. In asthmatic subjects histamine at a mean Four diabetic subjects (female) with severe, symptomatic concentration of 0.2% decreased peak expiratory flow rate autonomic neuropathy and cardiovascular evidence of (PEFR) by 33%, and half time clearance of 99"mTc DTPA vagal denervation who took part in our original study were (T ½/2) by 41 %o. In normal subjects 0.2% histamine tested and compared with non-neuropathic diabetic decreased PEFR by only 9% but still decreased Tz/2 by subjects. All had normal resting lung function and were 44%. A higher dose of histamine in normal subjects on September 27, 2021 by guest. Protected non-smokers. Histamine was administered by tidal produced a decrease in PEFR of 56%, but no further inhalations from a Wright nebuliser in increasing change in T 1/2. Prior inhalation of salbutamol in normal concentrations from 2 mg/ml to 16 mg/ml. Specific subjects prevented changes in peak flow but not the airways conductance (sGaw) was measured before the increase in permeability produced by histamine. We challenge and at 20 second intervals between one and three conclude that the mechanisms of increased permeability minutes after the end of each nebulisation. The mean sGaw and bronchoconstriction produced by histamine are value was taken as the response to that concentration and probably independent and that increased histamine log dose-response curves were constructed. The responsiveness may apply to changes in airway calibre but concentration of histamine causing 35% fall in sGaw not to epithelial permeability. (PC35) was derived by interpolation. There was no difference in geometric mean PC35 between the subjects with neuropathy (9.6 mg/ml) and those without (10.3 Verapamil inhibits leukotriene D-induced mg/ml). We conclude that the action of histamine in the bronchoconstriction in normal subjects human airway is largely a direct effect on bronchial smooth muscle and that the bronchial tree of subjects with JA ROBERTS, MA GIEMBYCZ, IW RODGER, NC THOMSON The autonomic neuropathy is capable of responding normally mechanism of leukotriene D4 (LTD4) induced airway to direct stimulation. narrowing in man is unclear. In this study we have Thorax: first published as 10.1136/thx.40.3.209 on 1 March 1985. Downloaded from 218 Proceedings ofthe British Thoracic Society examined the effect of inhaled verapamil on the patients, mast cell changes during allergen induced rhinitis bronchoconstriction induced by LTD4 in six normal can be readily observed in this organ. Eight symptomless subjects (age 22-36) years). On separate days, after patients with allergic rhinitis (five females, three males; pretreatment with verapamil (2.5 mg/ml for S min) or mean age 24.4 years) were studied. Nasal biopsy samples placebo, each subject inhaled increasing concentrations of were obtained from each patients after an allergen solution LTD4 up to a maximum of 50 *g/ml. Aerosols of the drugs (lyophilised extracts reconstituted with isotonic saline) had were generated by a Wright nebuliser. Results were been nebulised into one nostril and a control solution expressed as the provocation concentration (PC) producing (isotonic saline) into the other. Biopsy samples were fixed in a 35% fall in specific airways conductance (PC35sGaw), Carnoy's solution, processed, and stained with a! naphthol and a 30% fall in flow at 30% of vital capacity as chloroacetate. Specimens were coded and randomised to determined from partial expiratory flow volume curves blind the investigator prior to examination by light (PC3OV30pP). Verapamil did not alter baseline sGaw or microscopy. Mast cells were counted in the epithelium and V30p). One subject failed to respond to LTD4 on either day. lamina propria and their integrity was assessed. Although In the other subjects PC35sGaw increased from 1.6 (0.6) no differences in mast cell numbers were found, the ,g/ml (geometric mean (SEM)) after placebo to 20.1 (1.1) percentage of degranulated cells after allergen provocation ,*g/ml after verapamil (p<0.01). PC30o'VXp) increased from (geometric mean (SEM) 91.4% (+ 2.9% - 2.8%) was 1.9 (3.2) pg/ml after placebo to 20.5 (1.6) yg/ml after significantly greater (p<0.02) than after administration of verapamil (p<0.01). These results demonstrate that the control solution (17.9% +4.7% -3.7%), providing verapamil has a protective effect against LTD4 induced direct In vivo evidence for mast cell activation. bronchoconstriction in man and they suggest that LTD4 acts, at least in part, through a verapamil sensitive, voltage dependent pathway. Neutrophil chemotactic activity In asthmatic reactions Induced by occupational exposure
Eosinophils and eosinophil major baic protein in allergen SR DURHAM, TH LEE, S LOCEWICZ, A DAVISON, PS BURGE, AJ induced late phase asthmatic reactions NEWMAN-TAYLOR, AB KAY We have previously shown that neutrophil chemotactic activity (NCA), a mast cell SR DURHAM, GJ GLEICH, D LOEGERING, AB KAY We have associated mediator was released after asthmatic reactions undertaken blood eosinophil counts and measurements of provoked by either specific (allergen) or non-specific plasma major basic concentrations protein (MBP) (by (exercise) triggers. We now report serum NCA copyright. specific radioimmunoassay) in 11 asthmatics with allergen determinations in subjects with occupational asthma. After induced dual reactions (DR), and in six subjects with single exposure the patients studied developed either immediate early reactions (SER). DRs were also subjected to a (IAR) or dual (immediate and late, DAR) asthmatic methacholine challenge on a separate control day. The DRs responses. Elevations in high molecular weight NCA had a significant increase in blood eosinophils at 24 hours (determined by Sephacryl S400 gel filtration) were observed
from 0.40 (0.08) (mean (SEM) x 109/litre) to 0.67 (0.10) in four laboratory animal handlers (three rat sensitive http://thorax.bmj.com/ (p<0.01). In contrast, there was no significant change in (IAR), one guinea pig sensitive (DAR)), and two subjects eosinophil counts for the SERs at any time point after sensitive to baker's flour (one IAR, one LAR) and challenge. In the DRs the methacholine PC20 (which ranged accompanied the reductions in FEV1. Four individuals with from 0.45 to 32 mg/ml) correlated inversely with baseline reactions to colophony (DAR) and one challenged with eosinophils (r= -0.61, p<0.05) and with the change in pulverised fuel ash (LAR) also had release of NCA. In eosinophils 24 hours after allergen (r= -0.81, p<0.01). contrast, NCA was not observed in subjects (one each) with Although MBP concentrations were elevated in asthmatic asthma after exposure to toluene diisocyanate (DAR), subjects (607 (59.5) ng/ml, cf control non-asthmatics 440 diphenyl methane diisocyanate (DAR), ammonium (25.4) ng/ml), there were no significant changes in MBP for hexacholoroplatinate (LAR), or phthalic anhydride (IAR).
the DRs for up to 24 hours after allergen inhalation. These These findings suggest that asthmatic reactions resulting on September 27, 2021 by guest. Protected results suggest that there is a relationship between non- from exposure to organic occupational agents were specific bronchial responsiveness, eosinophilia and late associated with HMW-NCA release, whereas these changes phase reactions. were not found in subjects challenged with small inorganic agents. The mechanisms of asthmatic reactions induced by occupational type bronchial provocation seem likely to be Direct evidence for mast cell involvement in type I allergic heterogeneous. reactions in man
OJ CORRADO, E GOMEZ, DL BALDWIN, AR SWANSTON, RJ Enhanced neutrophil and monocyte cytotoxicity after DAVIES The relative inaccessibility of the lower airways exercise induced asthma has prevented the direct in vivo study in man of mast cell activation during allergic asthma, and our current concepts R MOQBEL, SR DURHAM, M CARROLL, AJ MacDONALD, GM of the mechanisms concerned are based largely on the WALSH, JUDITH MacKAY, RJ SHAW, AB KAY We previously indirect measurement of mediator levels in peripheral blood demonstrated that mast cell associated mediators were after allergen provocation. As it is possible to take biopsy released after exercise induced asthma (EIA) and that this specimens of the nasal mucosa lining the inferior turbinate in turn was followed by leucocyte activation as shown by under local anaesthesia with minimal discomfort to the enhanced expression of membrane receptors. In the present Thorax: first published as 10.1136/thx.40.3.209 on 1 March 1985. Downloaded from Proceedings of the British Thoracic Society 219 study we have established that neutrophils and monocytes with anti-IgE, histamine release from monkey are functionally altered after EIA as shown by an enhanced bronchoalveolar lavage cells was inhibited preferentially by cytotoxic activity. The cytotoxic assay system employed nedocromil when compared with sodium cromoglycate. In was leucocyte killing of helminthic larvae in vitro man nedocromil also inhibited allergen and exercise (schistosomula of schistosoma mansoni). In eight asthmatic induced asthma. In a double blind crossover study three patients there was a time dependent increase in the doses of nedocromil (2, 1, and 0.5 mg) were compared with cytotoxic capacities of both neutrophils and monocytes for placebo in 10 asthmatic subjects undergoing allergen up to 60 minutes after treadmill exercise. The increases in challenge. There was a statistically significant dose the ability of these cells to kill helminthic larvae was dependent inhibition of the allergen induced fall in FEVY accompanied by enhancement of complement receptors and (p<0.05). In a further eight subjects the compound was preceded by elevations in serum neutrophil chemotactic shown to inhibit exercise induced asthma with a significant activity and reductions in FEVI. These changes were reduction in the fall in FEVY after nedocromil when inhibited by prior administration of sodium cromoglycate, compared with placebo (p<0.01). but were not observed in five asthmatic patients in whom asthma was not induced by an identical exercise task. These studies indicate that EIA leads to enhancement of the Human alveolar macrophages express the a1I proteinase cytotoxic capacity of neutrophils and monocytes, findings Inhibitor gene that may be relevant to tissue destruction by inflammatory cells in asthma. PA BOYD, ND HASTIE, NE WOOD, AP GREENING Phagocyte derived proteinases may be responsible for acute and chronic lung tissue injury. In general, the lung parenchyma Factors predisposing to exercise induced late asthmatic is protected from such proteolytic damage by an response antiproteinase screen, to which aI proteinase inhibitor (al-Pi) is a major contributor. ai-Pi is the principal serum TH LEE, H INUI, T NAGAKURA, Y IIKURA Seventeen children antielastase and enters the bronchoalveolar secretions by developed reproducible early (5-15 min) and late asthmatic diffusion. The protein is synthesised by hepatocytes. In responses (3-12 h) (dual reactions) after cycle ergometer vitro data, however, have suggested that human monocytes exercise. The coefficients of variation in percentage and rat alveolar macrophages also are capable of decrease in FEVy during early and late reactions were 23% synthesising small amounts of ai-Pi. We have examined and 28% respectively. There was significant correlation the ability of human alveolar macrophages to express the copyright. (r = 0.62, p<0.01) between the magnitude of their early and alPi gene. Alveolar macrophages were obtained by late reactions, emphasising the direct relationship of these bronchoalveolar lavage at diagnostic bronchoscopy. The responses. Similar changes in pulmonary function were not RNA was extracted by guanidine isothiocyanate and seen on a control day. No significant differences were centrifugation over CsCI. The presence of a 1-Pi mRNA observed in the clinical severity of asthma, diurnal was determined by hybridisation on nitrocellulose filters variations in FEVI, and extent of the initial decrease in with a 32p nick translated human liver a I-Pi http://thorax.bmj.com/ FEV1 and 50 after exercise between the children with dual complementary DNA probe. Autoradiography of the filters responses and 19 children with single early reactions. These confirmed that human alveolar macrophages actively findings suggest that the occurrence of late reactions after transcribe the a l-Pi gene. This is highly pertinent to exercise is not determined by differences in severity of investigations relating to the proteolytic theory of the disease or baseline airway reactivity in asthmatic children. development of emphysema since it indicates that This view is supported by the demonstration that there was measurements of ct -Pi concentration activity in general no significant difference in the dose of inhaled bronchoalveolar secretions may not give a true indication acetylcholine necessary to elicit a 20% decrease in FEVY in of its activity in the local microenvironment of the terminal eight children with dual responses (499 (SD) 130) *g/ml) and respiratory bronchioles which are sites of macrophage and seven children with a single early reaction (333 (64) clustering. on September 27, 2021 by guest. Protected pg/ml) after exercise. The rate of spontaneous recovery from early reactions was significantly (p<0.01) slower in children with dual responses, suggesting that this variable Serum factors and proteinase Inhibitors modify alveolar may predict the development of late phase reactions in macrophage release of reactive oxygen species exercise induced asthma. NE WOOD, DC FLENLEY, AP GREENING Extracellular release of reactive reduction products of oxygen by phagocytes can Nedocromil a mucosal and connective tissue mast cell cause lung tissue injury by direct (lipid peroxidation) and stabiliser, Inhibits allergen and exercise Induced asthma indirect (inhibition of antiproteinases) mechanisms. Alveolar macrophages from smokers, In vitro, release RJ SHAW, P YOUNGCHAIYUD, TSC ORR, E WELLS, B. GREENWOOD, greater amounts of superoxide (.02 and hydrogen peroxide TB LEE, AB KAY Nedocromil, the disodium salt of a (H202) than alveolar macrophages from non-smokers pyranoquinoline dicarboxilic acid, has a similar profile of (ARRD 1981;123: 85 and Clin Sci 1983;65: 661). In vitro activity to sodium cromoglycate (SCG) but appears to be however culture conditions may influence these metabolic considerably more active than sodium cromoglycate in functions of alveolar macrophages. We have examined the stabilising lung mucosal type mast cells obtained from non- extracellular release of *O- and H202 from alveolar human primates (macaque monkeys). After stimulation macrophages after overnight culture in three different Thorax: first published as 10.1136/thx.40.3.209 on 1 March 1985. Downloaded from 220 Proceedings of the British Thoracic Society media (RPMI 1640, MEM, medium 199) in the presence compared with 0.4% (0.05%)). The histamine content of and absence of newborn calf or autologous sera. Cells were 106 recovered cells was proportionally increased (18 (1.5) ng acquired by bronchoalveolar lavage from 52 patients at the compared with 5 (1.0) ng). Anti-IgE induced histamine time of diagnostic bronchoscopy. There was no consistent release was accentuated in patients with sarcoidosis, with pattern of response; some alveolar macrophages showed increased release of histamine at all dilutions of anti-IgE. enhanced H202 release after culture with serum containing The maximum mean (SEM) percentage histamine release in media and others the reverse. Since cell-surface proteinases controls was 20%o (1.8%7o) and occurred with an anti-IgE can modulate the functions of macrophages, we questioned dilution of 1/100. At this dilution of anti-IgE, patients with whether antiproteinases in the sera may have been sarcoidosis released a mean of 44%o (6%) (p<0.001). This responsible in part for this variation in release of H202 accentuation of histamine release at all dilutions of anti-IgE from alveolar macrophages in culture. We found that was significantly correlated with the percentage of preincubation of alveolar macrophages in medium lymphocytes recovered. It was independent of serum IgE containing either aIproteinase inhibitor or soybean trypsin concentration, lavage IgE concentration, and the atopic inhibitor led to an enhanced release of *O° and H202 on status of the patients, none of which differed between the stimulation of these cells. We therefore conclude that two groups. The accentuation of IgE dependent histamine interpretation of in vitro estimations of alveolar release appeared to be confined to the lungs as anti-IgE macrophages release of reactive oxygen species should take induced release from blood basophils was identical in both into account the culture conditions used. groups.
Are there enough oxygen centred free radicals in cigarette Alveolar macrophage phagocytosis in sarcoidosis smoke to produce emphysema in smokers? A GANT, I BARBOSA, B GREY, A HAMBLIN, NT BATEMAN, TC C BORLAND, T HIGENBOTTAM The oxidant theory proposes STOKES We have investigated the in vitro phagocytic that emphysema is due to unrestricted activity of elastolytic activity of pulmonary alveolar macrophages, obtained at enzymes resulting from the inhibition of antiproteases bronchoalveolar lavage in 25 patients with sarcoidosis and (Janoff, A J. Appl Physiol 1983;55:285-93). It has been 17 controls. Radiographically, three patients had stage 0 suggested that oxygen centred free radicals which have been disease, six stage I, 14 stage II, and two stage III. The detected in the gas phase of cigarette smoke by electron spin number of yeast particles (Candida guillermondii) resonance (Pryor WA et al. Environ Health Perspect phagocytosed per 100 alveolar macrophages was expressed copyright. 1983;47:345-55) may inhibit antiproteases by oxidation. as the phagocytic index (PI). There was a significant Nitric oxide (NO) normally found in smoke is rapidly difference (p<0.001) between the PI of patients whose oxidised by oxygen centred free radicals. Observing the rate duration of symptoms was less than eight weeks (mean (SD) of disappearance of NO from a gas mixture offers a means PI 401 (184)) and the PI of both patients whose symptoms of detecting these species. A popular king size middle tar were of longer duration (PI 115 (89)) and of controls (PI cigarette was smoked by drawing air continuously at I 135 (125)). Patients with stage I and II disease tended to http://thorax.bmj.com/ 1/min. The rate of disappearance of NO was measured by have a higher PI than stage 0 and stage III patients and the chemiluminescent method. Gas phase smoke and whole controls. PI did not correlate with serum ACE, alveolar T smoke were compared. The rate of disappearance of NO cells expressed as a percentage of total mononuclear cells, from filtered smoke followed first order kinetics with a half or T cell helper/suppressor ratios in the bronchoalveolar time of 4.4 minutes, favouring a reaction with oxygen lavage fluid at any stage of the disease. Increased centred free radicals. By comparison, in whole smoke NO phagocytic activity of the alveolar macrophages may disappeared at a slower rate with a rate constant of represent an early event in sarcoidosis, although in this 9.5 x 103 12 mol-2 S- 1, conforming to second order study PI did not correlate with other markers of disease kinetics. This compares with the reaction rate of NO and activity. oxygen in air of 7.3 x 103 12 mol-2 S- 1. We conclude that on September 27, 2021 by guest. Protected oxygen centred free radicals are only active when particulates have been filtered from smoke. If emphysema Release of histamine and newly generated mediators from results from inhibition of antiproteases by oxidants, then human bronchoalveolar lavage cells cigarette smoke is not likely to be directly responsible. RM AGIUS, C ROBINSON, ST HOLGATE The release of inflammatory mediators from mast cells and other cells Hyperresponsiveness of bronchoalveolar mast cells in adjacent to the bronchial lumen and in the alveoli may play sarcoidosis an important role in the pathogenesis of asthma and parenchymal lung disease. We have investigated the release KC FLINT, B HUDSPITH, J BROSTOFF, KBP LEUNG, FL PEARCE, of the preformed mast cell mediator histamine and D G JAMES, N Mcl JOHNSON Bronchoalveolar lavage has been oxidative products of arachidonic acid from performed in 34 patients with sarcoidosis and 20 controls bronchoalveolar lavage cells activated by reversed undergoing bronchoscopy for routine diagnostic purposes. anaphylaxis and the calcium ionophore A23 187. After On the basis of the alcian blue safranin reaction the passive sensitisation with human myeloma IgE, challenge percentage of mast cells within the lavage population of of bronchoalveolar lavage cells with anti-human IgE patients with sarcoidosis was found to be significantly stimulated a maximum net release of histamine of 22%7o different from controls (mean (SEM) 2.0%/o (0.1%) (6%) (n = 5 mean (SEM)). A23187 caused a concentration Thorax: first published as 10.1136/thx.40.3.209 on 1 March 1985. Downloaded from Proceedings of the British Thoracic Society 221 related release of histamine of 0.1, 3.3 pjmol/l, the mean (three cryptogenic fibrosing alveolitis, one sarcoidosis). The maximum net release being 31% (5%) (n=9), maximum secondary alveolar lipoproteinosis in these four cases was release occurring two minutes following challenge. Calcium associated with current or recent (within six months) dependent stimulation of bronchoalveolar lavage cells also clinical deterioration. In the four cases the number of GAB stimulated a concentration related release of the pre preparation increased with the length of time that cyclooxygenase products TXB2 and PGD2 as well as patients had received corticosteroid therapy (n = 6, 5-lipoxygenase products. These data indicate that cells Spearman rs=1,p<0.01) and with increasingly high titres recovered by bronchoalveolar lavage have the capacity to of antibody to Pneumocystis carinii (n = 5, r,= 1, p<0.01). release large quantities of putative mediators which may be No pneumocystis organisms were found on Gomori relevant to the pathogenesis of inflammatory lung disease. staining of the bronchoalveolar lavage fluid. Lipoprotein in bronchoalveolar lavage may detect not only cases of idiopathic alveolar lipoproteinosis, but also secondary cases The identification and partial characterisation of a human arising in immunosuppressed patients. alveolar macrophage derived neutrophil activating factor
TH LEE, JE PENNINGTON, TH ROSSING, LW BOERTH Human Bronchoalveolar lavage and clearance of 99mTc labelled alveolar macrophages, obtained from eight normal DTPA in asbestos workers without evidence of asbestosis volunteers by bronchial lavage and cultured in monolayers, released an activity with the capacity to enhance AR GELLERT, JA LANGFORD, S UTHAYAKUMAR, RM bactericidal properties of human neutrophils in vitro. RUDD Recent work has shown that accelerated clearance I x 106 neutrophils pre-exposed to macrophage culture of inhaled 99mTc labelled DTPA correlates with supernatants for 15 minutes produced a significant dose percentages of bronchoalveolar lavage inflammatory cells dependent decrease in viable serum resistant Pseudomonas in asbestosis and may occur in asbestos exposed subjects aeruginosa when incubated with I x 107 bacteria for 120 without asbestosis (Gellert et al. Thorax 1984;39:709). We minutes as compared with neutrophils pre-exposed to performed bronchoalveolar lavage and measured the control buffer (p<0.02). The release of this activity (NAF) clearance of inhaled 99mTc DTPA in 20 non-smoking was dependent on the duration of macrophage culture, was subjects (mean age 50, range 36-38 years) occupationally stimulated by the presence of heat inactivated P aeruginosa exposed to asbestos (mean duration 14, range 3-30 years). but not by latex particles, and was inhibited by the presence All had normal lung function and none had evidence of of cycloheximide during culture. Physicochemical asbestosis. The mean bronchoalveolar lavage results were: copyright. characterisation revealed that NAF was 6000 d in size with a total cells per ml 737 x 103 (360-1210), 7o macrophages 79 pl of 7.6; it was stable to heating at 56°C for 30 minutes and (49-96), % lymphocytes 13 (1-42), % neutrophils 8 (1-40), was susceptible to inactivation by trypsin, chymotrypsin, % eosinophils 0 (0-3), asbestos bodies per ml 83 (0-550). In and neuraminidase in a time and dose dependent manner. contrast to normal bronchoalveolar lavage cell profiles NAF was only minimally chemotactic for neutrophils and reported in asbestos workers with no evidence of asbestosis did not increase the phagocytosis of 3 Pseudomonas. It (Bignon et al. Rev Fr Mal Respir 1978;6:353-8), we found http://thorax.bmj.com/ augmented superoxide anion generation by PMN during increased percentages of lymphocytes in eight subjects and phagocytosis and during submaximal stimulation by increased neutrophils in four others when compared with phorbol myristate acetate. These findings indicate that normal ranges in our laboratory. Higher percentages of human alveolar macrophages secrete a heat stable, low neutrophils correlated with longer duration of exposure molecular weight basic glycoprotein, which may participate (r = 0.54,p<0.025), and shorter time since last exposure to in pulmonary defences against infection by augmenting asbestos (r = 0.54,p<0.025). Although three subjects neutrophils' oxidative microbicidal activity. showed faster clearance of 99mTc DTPA than was observed in normal non-smokers in our laboratory, there were no relationships between isotope clearance and any Relevance of lipoprotein aggregates in bronchoalveolar bronchoalveolar lavage variables. Bronchoalveolar lavage on September 27, 2021 by guest. Protected lavage samples from patients with chronic widespread profiles in asbestos workers may be abnormal in the pulmonary shadows absence of clinical or radiological evidence of asbestosis. CFA PANTIN, A DEWAR, PL HASLAM In five of 736 patients with chronic widespread pulmonary shadows, large Immunohistological analysis of lung tissue in cryptogenic "globular" basophilic staining acellular bodies (GAB), fibrosing alveolitis 20-100 u diameter were observed among the cells obtained by small volume bronchoalveolar lavage. By electron DA CAMPBELL, LW POULTER, G JANOSSY, RM du microscopy each body appeared as phospholipid lamellae BOIS Cryptogenic fibrosing alveolitis is associated with an showing the typical regular periodicity seen in idiopathic immune hypersensitivity response but uncertainty exists alveolar lipoproteinosis. The bronchoalveolar lavage fluid regarding the contribution of different immunological was milky in two cases, but only one case showed on mechanisms (Crystal et al. N Engi J Med 1984;310:154). electron microscopy the small (2-5 u) lamellar bodies of Using monoclonal antibody and histochemical techniques wavy or regular periodicity and undifferentiated (Poulter et al. In: Immunocytochemistry today. Bristol: amorphous debris, also typically present in idiopathic Wright, 1983: 233), we analysed lung biopsies from six alveolar lipoproteinosis, and this diagnosis was confirmed patients with cryptogenic fibrosing alveolitis. The on biopsy. The other four cases had proved diagnoses predominantly mononuclear inflammatory cell infiltrate Thorax: first published as 10.1136/thx.40.3.209 on 1 March 1985. Downloaded from 222 Proceedings of the British Thoracic Society present contained subsets of lymphoid and non-lymphoid fibroblast replication and as a consequence increase lung cells. Most lymphoid cells were B lymphocytes organised collagen production. Rabbits were lavaged two, six, and 14 into follicles with occasional germinal centre formation. days after the intratracheal instillation of bleomycin or IgM was the major class of immunoglobulin expressed. saline alone and the cells obtained incubated for 24 hours at Both T4 and T8 positive lymphocytes were distributed 106 viable cells per ml of medium containing 21% serum. diffusely throughout the interstitium. T4 positive cells were The growth promoting activity of the supernatant was also seen within B lymphoid follicles as were dendritic tested on a rabbit lung fibroblast line (R9ab) by a reticulum cells. Germinal centre formation within the lung photometric method for measuring cell numbers by staining interstitium suggests that a local B cell immune response is with methylene blue. Total viable cell yields in lavage from occurring in cryptogenic fibrosing alveolitis. Most non- bleomycin animals were (mean (SEM): 36.2 (6.5) x106, lymphoid cells expressed a phenotype characteristic of 47.5 (2.4)x 106, and 71.6 (14.8) x 106 at two, six and 14 inflammatory macrophages. Nevertheless, the presence of a days respectively, compared with 14.5 (3.4) x 106 for small number of cells with the phenotype of interdigitating controls. Supernatants from control animals led to 19.1% cells, along with T lymphocytes of the helper subset (T4 (2.7%7o) higher fibroblast numbers than medium alone. positive), suggests that cell-mediated immune responses Those from lavage cells two, six and 14 days after may also be occurring. These data strongly support the idea bleomycin were 23.3% (3.3%) 17.8% (3%), and 21.0%7o that local induction of immune responses is central to the (3.107o) respectively. We conclude that, in this model of pathogenesis of this disease. pulmonary fibrosis, the overall alveolar burden of fibroblast growth promoting acitivity may be greater in the bleomycin animals by virtue of the greatest number of Progress of bleomycin induced lung fibrosis in rabbits inflammatory cells present but not because of an increased production per inflammatory cell. CM O'CONNOR, A O'BRIEN, E SWEENEY, MX FITZGERALD Intratracheal instillation of intratracheal bleomycin is a standard method of inducing lung fibrosis in Does nebulised bronchodilator aerosol droplet size matter? experimental animals. One drawback is the rapidity with which pathological changes occur. Laurent et al. (Eur J M CLAY, D PAVIA, S CLARKE Nebulisers generate aerosols of Clin Invest 1981;11:441-8) have suggested that fibrosis in varying sizes depending on make and driving gas flow rate. rabbits following intratracheal bleomycin evolves more We have measured large and small airways bronchodilation slowly than in other small laboratory animals. To further in seven asthmatics (6M, IF) after inhalation under copyright. examine this we assessed bleomycin treated (n = 18; single controlled conditions of 2.5 mg terbutaline sulphate as intratracheal dose of bleomycin in 10 mg/kg body weight) nebulised aerosols of three different size distributions. In a and control (n = 12) rabbits with respect to a range of randomised single blind manner the patients underwent a biochemical and morphological indices of fibrosis. Animals control run or inhaled aerosols of mass median diameters had blood sampled at weekly intervals and were sacrificed (MMD) 10.3, 4.6, or 1.8 pm. FEV1, FVC, PEFR, http://thorax.bmj.com/ four or eight weeks after treatment. No change in lung Vmax50and Vmax25 were measured before and over two composition was observed four weeks after treatment but hours following the aerosol inhalations. Results of all tests histological examination revealed pulmonary inflammation (except FVC) significantly improved (p<0.02) over the in treated animals at this stage. By eight weeks the total control run during the two hours after aerosol treatment. lung content of DNA, protein and collagen were elevated, The percentage increase in small airways function assessed as were lung concentrations (jug/mg dry weight of protein by the Vmax25 was greatest after inhalation of the smallest and collagen (p<0.05). These results confirm that the aerosol: 203 (34)%7o at 30 minutes compared with 121 (37)o progression of fibrosis is slower in rabbits than in other and 116 (33)07o (mean (SEM)) after the 4.6 and 10.3 um small animals and thus more closely mimics the human aerosols. For the large airways the small aerosol had an condition. Notably, plasma ACE levels in treated animals equipotent effect to that of the larger aerosols. The results on September 27, 2021 by guest. Protected decreased by 20%7o (p<0.01) one week after treatment, and indicate that a small aerosol droplet size (2 pm or less) then returned to normal. No such change occurred in might have a more beneficial effect on small airways controls. This suggests that changes in plasma ACE levels function than larger aerosols and nebulisers capable of may reflect early damage to lung tissue prior to the generating such fine aerosols should be used for optimum development of lung fibrosis. treatment.
Secretion of fibroblast growth promoting activity by lavage Is BCG vaccination still necessary in Edinburgh? inflammatory cells in bleomycin Induced pulmonary fibrosis in the rabbit S CAPEWELL, A FRANCE, N UZEL, AG LEITCH We have investigated the current value of BCG vaccination in MH OLIVER, PJ COLE, GJ LAURENT The intratracheal Edinburgh by relating tuberculosis notifications in older instillation of bleomycin into rabbits is known to cause a schoolchildren and young adults after routine Heaf testing rapid deposition of collagen but the molecular interactions and vaccination at school to the entire schools population leading to this change are poorly understood. In this study for the period 1970-83. Seventy seven new cases were we examined the possibility that a factor or factors notified in caucasians from a total schools population of produced by lavage inflammatory cells may affect about 89 000 observed for a mean period of seven years. Thorax: first published as 10.1136/thx.40.3.209 on 1 March 1985. Downloaded from Proceedings of the British Thoracic Society 223 The annual incidence of new cases in the 65 692 children difficulties arise in chronic renal failure because the vaccinated at school was 7/10. This was significantly less symptoms of the two conditions are similar, the than the 21/105 in 12 878 children who missed both Heaf tuberculosis is predominantly extrapulmonary chest testing and BCG vaccination and the 41/105 in 5 316 radiograph usually normal, and tuberculin reactivity is children who had been tuberculin positive at school (all commonly lost. Culture of biopsy material gives the highest p<0.001). The incidence of new cases increased diagnostic yield. A high index of suspicion is important significantly with the strength of the tuberculin reaction, since late diagnosis is associated with a poor prognosis: the from 6/105 in Heaf grades I and II to 422/105 in Heaf two patients with the most widespread disease died despite grades III and IV (p<0.001). The 5 316 tuberculin positive aggressive treatment. Chemotherapy is safe if used children had three chest radiographs, with detection of 10 carefully and effective if given early enough. Reactivation new cases; none were Heaf grade I. Approximately 1/1600 of tuberculosis should be considered in any uraemic patient radiographs were positive for Heaf grade II reactors, 1/230 who inexplicably deteriorates, particularly if he or she has a for Heaf grade III, and 1/75 for Heaf grade IV (p<0.001). history of tuberculosis or comes from an area where it is The efficacy of BCG was 65%, about 56 cases of endemic. tuberculosis being prevented by 66 000 vaccinations in 13 years. BCG vaccination continues to offer valuable protection against tuberculosis in Edinburgh. What is the value of TLCO estimation in patients with AIDS and persistent generalised lymphadenopathy? Lymph node tuberculosis: a controlled trial of nine versus DA HOLT, J WEBER, EE KEAL, AJ PINCHING Nineteen patients 18 months' chemotherapy with persistent generalised lymphadenopathy had a reduced TLCO (mean 77.1 % predicted), with normal chest CR McGAVIN FOR BRITISH THORACIC SOCIETY RESEARCH radiograph and spirometry. Three with symptoms of cough COMMITTEE One hundred and fity-two patients with or dyspnoea had fibreoptic bronchoscopy and lymph node tuberculosis were enrolled in a randomised trial transbronchial biopsy; they had normal chest radiographs, of nine versus 18 months' chemotherapy. Treatment blood gas tensions and gallium scans but lower TLCO values consisted of rifampicin plus isoniazid for nine or 18 months (68.7%). Only one had pneumocystis pneumonia, but supplemented initially by ethambutol for eight weeks. At 36 another died of it 10 months later; the third remains well. months data from 113 patients were available for analysis Eight additional AIDS patients had a mean TLCO of
58.4%. copyright. of whom 56 had received the short course regime. Progress Four out of six had pneumocystis pneumonia on during chemotherapy was uneventful in 74% of patients. transbronchialbiopsy. In one pneumocystis pneumonia Fresh nodes appeared in 14% and existing nodes increased patient the TLCO rose from 52% to 62% after successful in size in 12%, all these events occurring within the first therapy with co-trimoxazole, blood gas tensions and chest eight months in both groups. In 9% residual nodes were radiographs returning to normal. A patient with Kaposi's palpable at the end of chemotherapy. After the end of sarcoma had a normal chest radiograph and blood gases http://thorax.bmj.com/ chemotherapy further events, including node enlargment, but a TLCO of 62%; biopsy (in retrospect) showed appearance of new nodes, fluctuations, and sinus pneumocystis pneumonia. This became symptomatic with formation, occurred in 11 % of patients. These events abnormal chest radiograph and a fall in TLCO to 31% a occurred with much the same frequency in the two groups month later; pneumocystis pneumonia was confirmed on and did not result in an unfavourable outcome. No repeat transbronchial biopsy. All AIDS/persistent microbiologically proved relapse has occurred. Nine generalised lymphadenopathy patients tested were HTLV months' treatment with rifampicin and isoniazid, III/LAV seropositive. We conclude: I pneumocystis supplemented initially by ethambutol, is likely to be pneumonia may occur in AIDS/persistent generalised adequate for lymph node tuberculosis but confirmation lymphadenopathy patients with normal blood gas tensions,
must await a longer period of follow-up. and gallium scan. 2 low TLCO and symptoms may be on September 27, 2021 by guest. Protected indications for transbronchial biopsy. 3 AIDS/persistent generalised lymphadenopathy patients also have reduced The diagnostic problem of tuberculosis In uraemia: high TLco for other, as yet undefined, reasons. 4 relapse and incidence In ethnic minorities remission of pneumocystis pneumonia may be monitored by TLCO estimates. 5 baseline and serial TLco may be val- F CUSS, A LININGTON, B HULME We have diagnosed eight uable in AIDS/persistent generalised lymphadenopathy. cases of tuberculosis in patients with chronic renal failure in the last two years compared with only one in the previous 10 years. Strikingly, all were born abroad. Non-white Didymella exitialls: a cause of late summer asthma patients constitute an increasing proportion of patients on our dialysis programme (30% at present) and these cases of MG HARRIES, J LACEY, RD TEE, AJ NEWMAN tuberculosis represent about a quarter of this group. There TAYLOR Didymella exitialis is a saprophyte of grain, was no evidence of interpatient spread: six patients had primarily barley; its spores are released in the summer tuberculous adenitis, one miliary tuberculosis and only one months, particularly after rainfall. We have investigated pulmonary tuberculosis and positive sputum. Two patients four patients in whom D exitialis seems to be an important were diagnosed before starting dialysis, five on cause of their asthma. One of the four made twice daily haemodialysis and one on peritoneal dialysis. Diagnostic peak expiratory flow rate (PEFR) measurements while Thorax: first published as 10.1136/thx.40.3.209 on 1 March 1985. Downloaded from 224 Proceedings of the British Thoracic Society spore counts of D exitialis and Alternaria tenuis were endoscopy units suggested that nasal symptoms might undertaken during summer 1983. Falls in PEFR occurred follow the use of Cidex (Axon ATR et al. Lancet when D exitialis spore counts were increased. All four 1981;1093-4), this clear association between glutaraldehyde patients had immediate skinprick test reactions provoked exposure and asthma and rhinitis has not been reported by, and specific IgE antibody to, D exitialis and A tenuis. previously. Since no entirely suitable alternative Inhalation of a soluble extract of D exitialis provoked disinfectant exists for endoscopes, measures should be immediate asthmatic reactions in these four, but not in a taken to minimise exposure of staff to Cidex. skinprick test negative volunteer. RAST inhibition studies with D exitialis and A tenuis showed self and cross inhibition suggesting shared antigens. Of 34 allergy clinic Prevalence and effects of atopy in byssinosis patients, six had skinprick test reactions to both moulds, two only to A tenuis, and three only to D exitialis, D HONEYBOURNE, M FINNEGAN, CAC PICKERING A total of suggesting additional specific antigens. We believe D 324 patients with byssinosis of grades 2 or 3 were seen exitialis is a cause of late summer asthma. Its importance is consecutively in an occupational outpatient clinic. Their not known, but allergy to it may contribute to asthma mean (SD) age was 58.8 (10.0) years and 215 were female. reported after thunder storms. Skinprick tests were performed for house dust mite, grass pollen, aspergillus, cat fur, and control material. A positive reaction was taken as > 2 mm more than the control to one House dust allergen avoidance in adult asthma: a controlled or more of the antigens. Atopics had spent fewer years in trial total working in the cotton mill (p<0.006) and fewer years working in the carding area (p = 0.02) than the non-atopics. MJ WALSHAW, CC EVANS Most studies on house dust The atopics had a lower FEV I% predicted (60.5) than the avoidance in allergic asthma have been in children over non-atopics (71.4: p<0.01), with no significant difference short periods of time. A long term study of dust avoidance in cigarette consumption. The overall prevalence of atopy in adult asthma in the community was therefore designed. was 11.90%o which was signficantly less (p<0.001) than Twenty-five adult asthmatic patients who were strongly 21.1% found in a group of 1391 unselected subjects of positive to house dust on skin testing were entered into a similar age from the general population. Multiple linear dust avoidance programme in the community; they were regression analysis confirmed that atopy resulted in a lower compared with 25 matched controls. At one year 22 of the predicted (p<0.05). These results suggest that were in FEV,%o experimental and 20 of the control group still the atopic byssinotics cease working in cotton mills earlier than copyright. study. The experimental patients showed a reduction non-atopic byssinotics and that they are also unable to (p<0.001) in dust and mite levels in their houses and an remain in areas of high dust exposure (for example, improvement (p<0.01) in bronchial reactivity, as measured carding) as long as non-atopics. Atopy may confer a greater by histamine challenge. Those who were strongly RAST risk of a reduced FEVyI% predicted in byssinosis. positive (score 3 or more) to house dust mite antigen also had improvements in PEFR (p<0.05), FEVl/FVC http://thorax.bmj.com/ (p<0.02), IgE (p<0.05), IgG (p = 0.05), symptom score and use of treatment. Patients who were not strongly RAST Airways obstruction, asthma, and skin atopy in adult positive and the control group were unchanged. House dust coeliac disease allergen avoidance in the community is practicable and is associated with an improvement in the subjective and AJ WILLIAMS, P ASQUITH, DE STABLEFORTH Despite intense objective features of asthma in sensitive patients. interest in the association between various parenchymal diseases (notable fibrosing alveolitis) and adult coeliac disease the possibility of coexisting airways disease in adult Asthma and rhinitis after glutaraldehyde exposure coeliac disease has not been fully investigated. We have studied 76 adult coeliac disease patients (52 female), mean on September 27, 2021 by guest. Protected J OSMAN, OJ CORRADO, RJ DAVIES Glutaraldehyde, unlike age 41 years (range 16-75), by detailed clinical assessment, the chemically related formaldehyde, is not a recognised spirometry and flow-volume curve analysis. Skin cause of occupational asthma. It is used widely as a hypersensitivity was determined for 21 common allergens, disinfectant in hospitals as a 2% (weight for volume) including 16 foods. Results have been compared with those aqueous alkaline solution (Cidex). We have investigated for 81 age, sex, and smoking matched controls with non- four nurses working in endoscopy units who reported inflammatory gastrointestinal disorders. The symptom of respiratory symptoms after exposure to this agent. All were wheeze was more commonly reported in adult coeliac atopic and three had extrinsic asthma or rhinitis or both. disease patients (2901 v 1101., p<0.01) but sputum Objective confirmation of their histories was sought by production was no more frequent (16%o v 10%, p>0.5). controlled simulation of work exposure in a challenge Evidence of airways obstruction (FEVI/FVC<650o) was chamber. Forced expiratory volume in one second, forced found in 13 (1701o) adult coeliac disease patients and in no vital capacity, and nasal airways resistance were measured controls. Similarly, mean predicted values of expiratory at regular intervals for eight hours and symptoms were flow rates (PEFR, V50, V25*) were all consistently lower recorded. One nurse developed a late asthmatic response *(p<0.001) in adult coeliac disease patients than those of and in a second nurse a dual nasal response was identified. controls. Altogether 15 (2001o) adult coeliac disease patients No symptoms or objective changes occurred in the other had asthma compared with three (4%0) controls (p<0.01). two nurses. Although a questionnaire survey of British Positive skinprick responses to food and environmental Thorax: first published as 10.1136/thx.40.3.209 on 1 March 1985. Downloaded from Proceedings of the British Thoracic Society 225 allergens were more common in adult coeliac disease 24 months in those with initial RVEF > 0.48 (Cox's patients (45 o compared with 27%7o controls, p<0.05). Sixty survival model). The %o predicted FEV1, however did per cent of those adult coeliac disease patients with asthma significantly affect survival (p<0.0001). RVEF and PAP had positive skinprick responses. Positive skin reactions to were measured simultaneously in a similar group of 50 foods were usually associated with skin hypersensitivity to patients with chronic bronchitis and emphysema (age 40-80, other environmental allergens and rarely occurred in Pao2 4.5-8.8 kPa, Paco2 5.1-8.6 kPa). RVEF (0.17-0.61) isolation (4qo of cases). did not correlate with PAP (10-60 mm Hg; r= -0.15, p>0.05. In 20 patients however, who also had simultaneous measurement of pulmonary vascular Sleep deprivation reduces overnight bronchoconstriction in resistance index (PVRI, dyn s cm - 5m - 2), we found a weak asthmatic patients correlation between RVEF and PVRI (r = - 0.45, p<0.05). We conclude that a single measurement of RVEF cannot GB RHIND, JC CATTERALL, IC STEWART, C SHAPIRO, NJ predict survival or PAP in patients with chronic bronchitis DOUGLAS It is unclear whether sleep causes nocturnal and emphysema but may indicate right ventricular asthma (Lancet 1983;1:220). We compared overnight afterload. changes in peak flow rate (PEFR) on two nights, seven to 14 days apart, one when the patients slept and another when they were kept awake (proved by EEG). The order of Transpulmonary formation of angiotension II in chronic nights was randomised. We studied 12 asthmatics (8M,4F; stable cor pulmonale 22-58 years) with nocturnal wheeze. During the sleep night they slept undisturbed and PEFR was recorded only at 10 JB NEILLY, CJ CLARK, AC TWEDDEL, AP RAE, D MCINTYRE, IH pm, 7 am, and before inhaler use if a patient awoke wheezy. HUNTON, JJ MORTON, RD STEVENSON The oedema associated On the deprivation night PEFR was recorded hourly. The 7 with cor pulmonale may be related to disturbance of the am PEFR were compared, although in five patients who renin-angiotensin system. In an attempt to investigate used inhalers on the sleep night preinhaler PEFR was pulmonary converting enzyme (CE) activity in chronic compared with the time matched PEFR on the sleep alveolar hypoxia we have studied formation of angiotensin deprivation night. All patients developed II across the lungs in 11 patients with stable cor pulmonale bronchoconstriction on both sleep and sleep deprived and type II respiratory failure. Transpulmonary nights (p<0.001). The 10 pm PEFRs were similar (sleep 418 angiotensin II formation rate was less than normal (mean copyright. (SEM 40) 1/min, deprivation 465 (43) I/mins; NS). The (SEM) 29.8 (12.4), normal 40 pmol/litre). After oxygen the absolute PEFR was lower after sleep than after sleep angiotensin formation rate increased significantly (40.4 deprivation (270 (46); 371 (43); p<0.01). The absolute and (14.2) pmol/l; p<0.01). This increase was independent of percentage falls in PEFR were greater after sleep (148 (28), changes in pulmonary blood flow or vascular resistance, 84 (13) 1/min; p<0.02; 38%o (6), 20q7o (4qo); p<0.01). suggesting a direct effect of oxygen on pulmonary CE Morning bronchial reactivity was the same after sleep and activity. Plasma angiotensin I concentrations were normal http://thorax.bmj.com/ sleep depirvation. This study extends previous observations (19.1 (1.8) pmol/l, normal 21.8 (2.4) pmol/l; p>0.05) and (Thorax 1979;34:749) showing that overnight serum angiotensin converting enzyme (SACE) levels were bronchoconstriction occurs despite EEG documented sleep reduced (12.8 (1.6), normal 15-30 units/I). There was no deprivation, but that the degree of bronchoconstriction is correlation between SACE levels and the magnitude of reduced when patients are kept awake. This suggests that transpulmonary angiotensin II formation. In conclusion, sleep influences circadian changes which cause nocturnal pulmonary CE activity is impaired in chronic alveolar asthma. hypoxia and improves with oxygen. This may be due to a direct effect of oxygen on pulmonary converting enzyme function. on September 27, 2021 by guest. Protected Significance of a single measurement of right ventricular ejection fraction in patients with chronic bronchitis and emphysema Chronic cor pulmonale: hormones and haemodynamics at rest and on exercise before and after nifedipine AJ FRANCE, KL PRINCE, RJ PRESCOTT, AL MUIR, W MACNEE, DC FLENLEY An elevated pulmonary arterial pressure (PAP) NJ EBEJER, H SINGH, DA HIGGINS, ML FORSLING, AH and associated cor pulmonale in patients with chronic HENDERSON, IA CAMPBELL We studied nine patients in cor bronchitis and emphysema indicates a poor prognosis. pulmonale secondary to chronic airflow limitation, to Right ventricular ejection fraction (RVEF) can be measured document humoral changes and haemodynamics at rest and by gated blood pool radionuclide ventriculography on exercise before and after nifedipine. Haemodynamics (normal,0.48). To determine whether RVEF can predict and hormone sampling were done at rest and during survival we have followed 44 patients with chronic dyspnoea limited bicycle exercise before and one hour after bronchitis and emphysema for two years (age 40-81, FEVy sublingual nifedipine (20 mg). Mean (SEM) resting levels of 0.2-1.7 1 Pao2 4.7-10.3 kPa, PaCo2 4.5-10.8 kPa, RVEF noradrenaline (459 (165) pg/ml) and adrenaline (166 (106) 0.24-0.66). Twenty-eight of these patients received pg/ml were normal. Renin (3.32 (1.11) pmol/ml/h), conventional treatment without domiciliary oxygen. aldosterone (533 (374) pmol/ml), and vasopressin (0.40 Eighteen of these 28 had RVEF <0.48; their median (0.24) U/ml) were raised. All hormone levels rose with survival was 18 months, not significantly different from > exercise as in normal subjects (by 276%, 172%o, 1607o, Thorax: first published as 10.1136/thx.40.3.209 on 1 March 1985. Downloaded from 226 Proceedings of the British Thoracic Society 127%, and 250%o respectively). Plasma sodium and gases during breathing nanoeuvres. We have developed osmolarity remained normal. Nifedipine reduced mean automated methods using slow exhalation and rebreathing pulmonary and systemic pressure by 14% and 19% which can simultaneously provide estimates of TLCO, respectively at rest and by 23% and 19% on exercise. It pulmonary capillary blood flow (Qc), and lung tissue increased cardiac output by 30% from 5.18 (1.50) I/min at volume (Vt). We studied eight normal subjects using a gas rest but did not alter it at maximum exercise. It reduced mixture of 2.5% sulphur hexafluoride, 1.2% acetylene, pulmonary and systemic vascular resistance by 32% and 0.3% C80, and 21% oxygen in nitrogen. For the slow 39% at rest and by 28% and 20% on exercise. It had no exhalation each inhaled from residual volume (RV) the gas effect on maximum exercise tolerance or oxygen delivery. mixture to total lung capacity (TLC) and then, with no Nifedipine thus reduced pulmonary artery pressure at rest breath hold, slowly exhaled at approximately 30 I/min. and during exercise without adverse effect. It had little Rebreathing was performed after a partial expiration and effect on resting hormone levels but increased the exercise then an inhalation of 50% of vital capacity (VC). Expired increment of renin and vasopressin to 4401 and 370% gas concentrations were measured with a MGA 200 respectively. spectrometer and an Apple II plus microcomputer. All measurements were performed in duplicate and two factor analysis of variance was used to compare results. Means were not significantly different (p>O.05; df 16:1). The Effects of reversing polycythaemia on the renin-anglotensin reproducibility of these measurements suggests that these system in patients with hypoxic cor pulmonale techniques may offer enhanced alternatives to the standard measurement of TLCO with breath hold, as they provide PJW WALLIS, JD FEW, AC NEWLAND, DW EMPEY Lowering more measures of lung function. blood viscosity by reversing polycythaemia diminishes renin secretion in the dog (McDonald KM. Circ Res Mean results with coefficient of variation (CV) 1974;34:112-22). We have observed the effects of reducing packed cell volume on plasma renin activity and plasma Methods TLCO (cv) 6c (cv) Vt (cv) aldosterone levels in 10 patients with secondary Slow exhalation 8.5 si(6.501o) 5.77 U/min(13.S%) 312(mls)(3.9%) polycythaemia and hypoxic cor pulmonale. A reduction in Rebreathing 7.9 si(ll.9%e) 5.77 U/min(7.70o) 279(mlsX3. lo) plasma renin activity and plasma aldosterone may usefully diminish fluid retention in such patients. The patients studied were normotensive with no renal impairment. copyright. Sodium intake (mean 100 mmol/24 h) and diuretic therapy remained constant during the investigation. Mean (SEM) packed cell volume was lowered from 0.62 (0.02) to 0.50 A rapid gas dilution method for measuring lung volumes in (0.02) by erythrapheresis with significant reductions in airflow obstruction blood viscosity at shear rates 23/s and 230/s respectively http://thorax.bmj.com/ (p<0.001). Plasma renin activity and plasma aldosterone HA JONES, EE DAVIES, JMB HUGHES The conventional helium were measured for four days before and after the (He) dilution method of measuring lung volume is lengthy procedure. Blood volume and renal blood flow were (>300 seconds) and may be inaccurate when gross assessed before and three days afterwards. Mean plasma maldistribution of ventilation is present. By reducing the renin activity (3450 (889) pg/ml/h) and plasma aldosterone circuit volume to 0.75 1 and by developing a mathematical (623 (132) pmol/l) were both raised. Plasma renin activity extrapolation to obtain the final equilibrium He did not change significantly after packed cell volume concentration before it has actually occurred, we have reduction and no sustained fall occurred in plasma reduced the rebreathing time to 20 seconds. A correction aldosterone. Mean blood pressure (84 (3) v 76 (3) mm Hg, was made on a breath by breath basis for the shrinkage of
p<0.01), blood volume (77 (4) v 67 (3) ml/kg; p<0.01), volume which occurs during the manoeuvre. Seven patients on September 27, 2021 by guest. Protected and renal blood flow (660 (38) v 597 (34) ml/min/1.73 M2; with asthma (mean FEV, 56%o predicted) and three with p<0.05) all fell significantly. In conclusion packed cell emphysema (mean FEV, 21%o predicted) rebreathed 10% volume reduction produced several important He, 10% SF6, and 30%o 02 in A from an 0.75 1 bag for 20 haemodynamic changes with opposing effects on renin breaths, followed by an inspiration to total lung capacity secretion. These conflicting events may explain the (TLC). Breath by breath He, SF6, 02, CO2, A and N2 unaltered plasma renin activity and plasma aldosterone concentrations were measured by mass spectrometry. The levels observed after reduction in blood viscosity by manoeuvre was repeated after aerosolised salbutamol (200 erythrapheresis. *g), when the mean FEV, had increased by 27% (SD 19/o). The TLC from He dilution was compared with TLC from body plethysmography. Before salbutamol the He/plethysmographic TLC ratio was 0.79 (0.18) without Simultaneous measurement of TLCO, pulmonary capillary and 0.95 (0.14) with extrapolation. After salbutamol ratios blood flow, and lung tissue volume were 0.85 (0.22) without and 0.95 (0.17) with extrapolation. Helium approached equilibrium faster after salbutamol, A FORESI, D SHAW, R PISTELLI, T HIGENBOTTAM With the but prediction of the TLC from the extrapolated He widespread use of microcomputers and mass spectrometers equilibrium appears to be equally valid before and after it has become possible to automate the analysis of multiple bronchodilatation. Thorax: first published as 10.1136/thx.40.3.209 on 1 March 1985. Downloaded from Proceedings of the British Thoracic Society 227 "Colonising microbial load": a cardinal concept in the Pneumonia in the acquired immune deficiency syndrome pathogenesis and treatment of progressive bronchiectasis (AIDS) due to "vicious circle" host mediated damage CR SWINBURN, AL POZNIAK, KC FLINT, N McI JOHNSON From P COLE, D ROBERTS, E HIGGS, C PRIOR Attempts by clinicians August 1983 to August 1984 we investigated and treated 10 and microbiologists to incrimate a pathogen as episodes of pneumonia in nine male homosexual patients "responsible" for chronic bronchial sepsis are frequently (mean age 36, range 25-41 years) with AIDS. The mean frustrated because the microbial flora colonising such duration of respiratory symptoms was 14 days (range 1-28 patients is usually varied, relatively avirulent, and less days). The presenting respiratory symptoms and signs were actively damaging to the host than it is passively damaging breathlessness (6), dry cough (9), productive cough (1), (by evoking a tissue damaging "vicious circle" focal crackles (2), scattered crackles (5), and clear chest (3). inflammatory response which is the host's unsuccessful Fever was present in nine patients. All the patients were attempt to clear it). We have measured "colonising hypoxaemic. The radiological appearance varied between a microbial load" (CML) in 25 patients treated over a year clear chest radiograph (1), focal abnormality (3), and for acute exacerbations of bronchiectasis with 3 g twice bilateral abnormality (6). The patients underwent fibreoptic daily oral amoxycillin and compared it with that in 11 bronchoscopy, bronchoalveolar lavage (BAL), and similar, but more severely affected, patients treated with 3 g transbronchial biopsy (TBB) (9 episodes). Pneumocystis oral amoxycillin twice daily for six months. The continuous carinii was identified in five patients by TBB and in a sixth, therapy resulted in greater and more sustained reduction of in whom TBB was negative despite a high clinical and CML than did that for exacerbations only - and was radiological suspicion of infection, by percutaneous lung associated with greater improvement in the clinical biopsy. P carinii was not seen in BAL aspirates. The parameters of sputum volume and spirometric values. organisms believed responsible in three other cases were These results suggest that CML is of central importance in Streptococcus pneumonia (2) and Pseudomonas aeruginosa provoking host mediated inflammation responsible for (1); no firm diagnosis was made in the remaining case. symptoms. We suggest that the treatment of severely Pneumocystis infection was not associated with focal progressive bronchiectasis should be reconsidered in terms radiological abnormality and the length of respiratory of reducing CML as completely as possible and for as long history was in general longer than in the cases of bacterial as possible to break the "vicious circle" of host mediated pneumonia. Three patients died in hospital of the inflammation and tissue damage. pneumonia, and seven were discharged. However, all the patients (5) who presented before June 1984 are now dead. copyright. Our findings are therefore in line with larger series from the USA. Factors affecting survival of adult patients with cystic fibrosis
Multicentre study of the effects of oral N-acetylcysteine in http://thorax.bmj.com/ ME HODSON, AE WISE, F DUNCAN, JC BATTEN Two hundred patients with chronic bronchitis and severe airways and ninety-one patients, 161 male and 130 female, over 16 obstruction years of age have attended the Brompton Hospital since 1965. Actuarial probability of survival to 25 years is 0.58, JT MACFARLANE FOR THE BRITISH THORACIC SOCIETY to 30 years 0.37, and to 35 years 0.30. Presentation with RESEARCH COMMITTEE Oral N-acetylcysteine (NAC) chest symptoms did not affect survival but those patients significantly reduces exacerbation rates and days lost from presenting with meconium ileus had a poorer survival than work in patients with chronic simple bronchitis (Boman G the others (0.001)? Patients who developed chest symptoms et al. Eur J Respir Dis 1983;64:405-15; Multicentre Study late survived longer - for example, those with symptoms Group. Eur J Respir Dis 1980;61,Suppl 111:93-108). We before 4 years survived less than patients developing report the results of a six month multicentre study of the on September 27, 2021 by guest. Protected symptoms after 4 years (0.001). Regular daily sputum effects of NAC on patients with chronic bronchitis production before 4 years was associated with reduced complicated by significant and irreversible airways survival for example 0.5 survival from 29 years to 23 years obstruction (FEV1<500% predicted). Two hundred and (0.001). The presence of Haemophilus influenzae or forty-four patients entered the study during October and Staphylococcus aureus in the sputum did not reduce November 1983. All took placebo sachets for one month. survival but Pseudomonas aeruginosa in the sputum did - One hundred and eighty-one completed this satisfactorily for example, 0.5 survival from 26 years to 22 years (0.001). and were then randomised to receive either active drug Survival was not affected by malabsorption, diabetes, or (NAC - FABROL 200 mg three times a day) or matching haemoptysis but was affected by pneumothorax and right placebo sachets for five months in a double blind parallel heart failure - for example, 0.5 survival from 29 to 24 group study. The two groups matched satisfactorily; the years (0.001) and from 34 to 22 years respectively (0.001). mean FEV1 for the 85 in the active group was 29% At age 16 years weight less than 90% predicted (0.01), FEVY predicted compared with 31% predicted for the 96 in the (0.001), and forced vital capacity less than 75% predicted placebo group. Patients kept detailed symptom diaries and (0.01) appeared to be adverse prognostic features. were assessed monthly. At the end of the study period, although the outcome in the active group appeared better *p values refer to maximum separation of curves for a given the differences did not reach conventional levels of feature irrespective of age. significance for the mean (SD) number of exacerbations Thorax: first published as 10.1136/thx.40.3.209 on 1 March 1985. Downloaded from 228 Proceedings of the British Thoracic Society
(2.1 (0.2) for active 2.6 (0.2) for placebo;p = 0.08), days dose-response relationship has been demonstrated (2) that spent in bed (4.8 (0.8), 5.1 (I.1);p=0.9, days on antibiotic the time course could not be assessed since the duration of (13.5 (1.7) 18.0 (2.8); p = 0.17), number of withdrawals (13; treatment was too short to allow a plateau of PEFR to 20; p = 0.4), incidence of side effects (which were few), drug occur. compliance (which was good), or the patients' assessments of the treatment. No difference emerged when subgroups were analysed according to the severity of the airways Serum angiotensin converting enzyme In the diagnosis and obstruction or the presence of treated cardiac failure. evaluation of pulmonary sarcoidosis PR STUDDY, R BIRD, DG JAMES It is generally accepted that Intramuscular triamcinolone in chronic severe asthma serum antiotensin converting enzyme activity may be increased in sarcoidosis. In our experience 85% of active DT MCLEOD, S CAPEWELL, A SEATON Patients with asthma pulmonary sarcoidosis patients have elevated SACE with who remain symptomatic in spite of regular, large doses of the highest activity in those with extensive pulmonary prednisolone form a well recognized problem group. infiltration. The role of serial SACE measurements in Previous studies (Peake et al. Br J Dis Chest 1979;73:39; following patients with sarcoidosis is less clear. We have Willey et al. Thorax 1984;39:340) have suggested that therefore studied the relationship between synchronous intramuscular triamcinolone acetonide may have a role in SACE measurements and serial chest radiographs in 46 their management. We report a year long study of patients with active untreated pulmonary sarcoidosis who asthmatics requiring at least 10 mg of prednisolone daily in were followed for at least two years. Ninety-one separate which, on a double blind basis, they were treated with either episodes of radiographic change were identified. The intramuscular triamcinolone 80 mg monthly or oral radiographs were scored for hilar gland size and inflitration prednisolone 10 mg daily. A double dummy, six month on the basis of the ILO U/C 1971 classification. SACE was crossover design was used, response being measured in measured by fluorimetric methods (Friedland and terms of twice daily peak flow rate and symptom score and Silverstein). A significant (p<0.01) concordant change in monthly clinical and biochemical assessment. Eighteen of both parameters occurred in 91% (21/23) with radiographic 22 patients completed the study, the withdrawals being due improvement and in 71% (22/31) with deterioration. In 37 to myocardinal infarction (1), bronchial carcinoma (1), no radiographic changes were detected after one year's muscle weakness during treatment with triamcinolone (1), observation and in 601% (22/37) serial SACE measurements and refusal to continue during treatment with prednisolone did not fluctuate significantly. SACE significantly copyright. (1). During triamcinolone therapy the patients achieved (p 0.05) paralleled the extent of the disease on chest significantly higher peak flow rates (p<0.001) and FEVI, radiographs and fluctuations in enzyme activity usually lower symptom scores, and lesser use of supplementary preceded radiographic change. In conclusion, not only does prednisolone, together with weight loss and evidence of SACE help in coroborating a diagnosis of sarcoidosis but
increased adrenal suppression (p<0.05 in each case). serial measurement provides a useful and sensitive index for http://thorax.bmj.com/ Despite slightly more side effects with triamcinolone, 17 of following the clinical course of active pulmonary disease. the 18 subjects expressed a preference for this drug at the close of the study. Long term protection in pigeon breeder's disease using face masks Dose-response characteristics of oral corticosteroids in the treatment of exacerbations of asthma G BOYD, A WALKER Simple respirators have been shown to offer substantial protection during inhalation challenge in JR WEBB Ten patients with asthma were treated with patients with extrinsic allergic alveolitis. (Hendrick DJ, et different doses of prednisolone during three separate al. Thorax, 1981 ;36:917-921). Symptomatic pigeon fanciers on September 27, 2021 by guest. Protected exacerbations. Prednisolone was given in doses of 0.2, 0.4, with Pigeon Breeders Disease are routinely advised to wear and 0.6 mg per kg daily dosage for two weeks in a double adequate face masks when working with pigeons. Serial blind randomised order (equal to 14, 28, and 42 mg measurements of specific IgG antibody to pigeon globulin prednisolone daily in person weighing 70 kg). Patients (ELISA) and observations on clinical status were made over developing an exacerbation recorded peak expiratory flow a period of six months in 24 symptomatic fanciers. Thirteen (Wrights mini peak flow meter) twice daily for two days wore masks (Group A) and nine declined the advice given before starting a course of prednisolone and for the two and did not (Group B). Following introduction of a mask in weeks' duration of treatment. The results for the group Group A, the mean serum antibody levels to pigeon show: (1) The PEF continued to improve throughout the globulin decreased from 103 (± 11) ug/ml at three months two week treatment period at all three dosages. (2) The (p<0.05), to 38 (± 7) pg/ml at six months (p<0.01). After morning PEFR response to treatment demonstrated a 14 months in this group the value had stabilised at 34 (± 6) significant dose-response effect. The morning PEFR at the ug/ml (p<0.01). This fall in antibody conformed to an end of the two week treatment period of 0.6 mg (high dose) exponential pattern (r = 0.77) with TA/2 of 2.3 months. The was significantly higher than at the end of treatment with mean antibody level in Group B increased from 76 ( 16) 0.4 mg (medium dose) (p<0.001) and the medium dose pg/ml to 98 (± 19) pg/ml after 1 month and to 121 (±46) morning PEFR was correspondingly higher than the 0.2 mg pg/ml after 3 months (p<0.05). Long term mask usage (low dose) PEFR (p0.05). The conclusions are (1) that a protected significantly against inhalation of pigeon antigens Thorax: first published as 10.1136/thx.40.3.209 on 1 March 1985. Downloaded from Proceedings of the British Thoracic Society 229 and the resulting fall in specific antibody levels was PEFR. Case 1, a man aged 55 years, was a cigarette smoker associated with clinical recovery. with chronic productive cough, without symptoms of occupational asthma, seen at a factory survey. His PEFR record showed a reduction in minimum but not maximum Geographical distribution of notifications of tuberculosis in or mean PEFR during periods at work. Case 2 was a England and Wales in 1983 woman aged 46. She had developed asthma prior to starting work as a solderer, and her asthma was not worse when at JH DARBYSHIRE, SP BYFIELD, KM CITRON, MJ HUMPHRIES, AJ work. Her PEFR record also showed only a reduction in NUNN, W FOX The annual tuberculosis notification rate for minimum PEFR during work periods. In both cases England and Wales in 1983 was 13.2 per 100 000 but there examination of the recordings showed that the first were considerable geographical differences in rates, due in measurements of the day were made earlier on working part to the varying size of the population of non-white, days. Case 2, who measured her PEFR on waking when at particularly Indian subcontinent, ethnic origin, whose rates work, although waking at the same time on holiday delayed are very high. Of the administrative areas of England and getting up and making her first PEFR measurement for up Wales, Greater London, where 41% of all the patients of to two hours. The delay allowed recovery from the non-white ethnic origin lived, had the highest rate (28.4 per "morning dips" in PEFR and apparent improvement in 100 000). The rate for the seven metropolitan counties asthma while on holiday - "pseudo-occupational asthma. combined (in which 75% of the cases of non-white ethnic origin lived) was 21.9 per 100 000, more than three times the rate of 8.2 for the remainder of the country. In the London Gluten induced asthma in adult coellac disease boroughs high rates were associated with a high proportion of non-white cases (p<0.02), but there was no association AJ WILLIAMS, P ASQUITH, DE STABLEFORTH We have recently between the number of non-white patients in the boroughs found an increased prevalence of airways obstruction, and the notification rates in the white population. Indeed asthma, and skin atopy in adult coeliac disease. To three boroughs where 6007 of the patients were of white investigate this further 10 coeliac disease patients with ethnic origin had rates approximately three times the asthma (seven female, mean age 43 years) underwent a six- national average. Rates in the 403 local authorities varied week study. They continued a gluten free diet for three considerably and in some of them major differences weeks, changing to a high gluten diet for a further three between the 1978-79 and 1983 surveys were related to local weeks. Throughout, measurements of pulmonary function outbreaks of tuberculosis. (daily diary PEFR, FEV1, FVC, 4qO, V25, histamine PC20, copyright. serum immunological tests (RAST IgE, immunoglobulins, complement, immune complexes, gluten antibodies) Extrinsic allergic alveolitis due to antigen from a humidifier eosinophil count, and skin atopy (environmental and food at 15°C allergens) were monitored. In eight (80%o) patients there
was no deterioration in asthma control but in two (2007.) http://thorax.bmj.com/ AS ROBERTSON, PS BURGE, A WIELAND Two workers there was a worsening of airways obstruction, marked after developed classical extrinsic allergic alveolitis while three-five days with a maximum reduction in PEFR, of working in a printing works with a contaminated 260o and 2807o. Bronchial reactivity also increased as humidifier. Both had nodular shadows on their chest evidenced by falls of 750o and 5007 of PC20 from baseline X-ray, reduced gas transfer measurements, and more than levels in these two patients. Baseline asthma control took 70% lymphocytes in their bronchoalveolar lavage fluid and from one to five months to return. There was an increase in lung biopsy specimens showed alveolitis with giant cells and eosinophil counts in both affected patients, but there were cholesterol clefts. In both workers symptoms were no other distinguishing immunological changes. Additional reproduced by bronchial provocation tests with the challenges in these two patients gave the same results. We humidifier antigen. Unlike in previous reported cases, conclude that gluten is an important factor in precipitating on September 27, 2021 by guest. Protected where exposure was to domestic humidifiers working at bronchospasm in some patients with adult coeliac disease higher temperatures, challenge to thermophillic and that as the condition is characterised by a "leaky" gut actinomycetes in our two workers caused no reaction. We mucosa the possibility of food allergic mechanisms in the found no single strongly positive precipitating antibody to a causation of airways obstruction in these patients must be wide range of individual microorganisms cultured from the considered. humidifier (including Penicillium sp) that might account for the presence of considerable IgG antibody against the humidifier antigen. Acute asthma admissions in an Asian immigrant population Pseudo-occupational asthma JG AYRES In the last decade admissions to East Birmingham Hospital (EBH) for acute asthma have risen K VENABLES, A DAVISON, K BROWN, A NEWMAN TAYLOR Peak from 300 (1972) to 479 (1982) (+ 57.907) for all patients and expiratory flow (PEFR) records self recorded at two hourly from 54 to 101 in Asian patients ( + 8707). The population intervals for 28 days are now used routinely in the diagnosis of the East District of Birmingham (1981 census) was 201 of occupational asthma. The readings are examined and 467, 21 200 of whom were Asian (10.507). The prevalence summarised as daily maximum, minimum, and mean of asthma in Asian school children in Birmingham is 1.507 Thorax: first published as 10.1136/thx.40.3.209 on 1 March 1985. Downloaded from 230 Proceedings of the British Thoracic Society (Morrison Smith et al. Clin Allergy 1971;1:57) compared by two separate operators have been compared with these with 4.3%o for Europid children and about 3%o for Europid from samples taken simultaneously and assayed by a adults in the UK. In 1981 (census year) there were 367 fluorescent polarisation immunoassay (AbbotTDX). The admissions for acute asthma in non-Asians and 104 in correlation with the reference assay was 0.99 and 0.98 Asians to EBH, representing an admission rate/1000 respectively (p<0.001), with 95% confidence limits of 0.3 asthmatics of 67.9 and 327 respectively (respective pg/ml. The coefficient of variation for repeated prevalence rates taken as 3%0 and 1.5%). Thus Asians were measurements was about 5%lo. These results suggest that this admitted 4.8 times more readily than non-Asians; their method may be useful for rapid estimation of theophylline mean hospital stay was slightly shorter than that of non- concentrations in the clinic or in research, even when used Asians (5.5 v 6.6 days), suggesting that their asthma may by relatively inexperienced operators. not be more severe, although this requires verification. The results suggest that asthma in Asians is less well controlled, probably owing to poor treatment compliance resulting in Slow release theophylline in preschool asthma turn from a combination of inadequate education, communication problems, and cultural attitudes to both BG LOFTUS, JF PRICE, (sponsored by JF COSTELLO) Slow release asthma and to having to take regular treatment. theophylline is widely used in the management of childhood asthma. Although dosage schedules have been recommended, few studies have assessed the drug in the Computer-aided prescribing of theophylline preschool age group. Over a nine-month period 49 preschool children with chronic asthma (age range 1 year 6 on MD PEAKE, H CHRYSTYN, BA MULLEY Despite the efficacy of months-S years 9 months) were started slow release oral theophyllines in asthma, careful monitoring is needed theophylline with a recommended regime. Mean (SD) initial to strike a balance between efficacy and safety. We have dosage was 18.1 (2.3) mg/kg/day in two doses. Blood levels developed a computer-based system for the therapeutic ranged from 3 to 21 mg/l (mean (SD) 9.1 (4.1)). The dosage monitoring of theophyllines (and other drugs) on a routine was increased in 23 children because of subtherapeutic basis in a busy district general hospital. An initial estimate blood levels. Eight patients were non-compliant - four is made of the patient's pharmacokinetic parameters denied non-compliance and four patients refused to take the preparation. Sixteen stopped therapy because of side (volume of distribution (VD) and elimination half life (t1/2e) and a simple nomogram being used. This can be effects. Six had behavioural problems, nine vomiting particularly, copyright. refined by the measurement of a single serum level of one nightmares. Symptoms resolved when the drug was withdrawn. Thirteen had satisfactory control of asthma. theophylline and with Bayesian statistical methods, revised of estimates being made of VD and t0/2e. For example, in a Twelve were deemed treatment failures because recent study using Uniphyllin we found an improvement in persisting symptoms, hospitalisation, or repeated courses prediction error (predicted minus measured) for serum of steroids. Outcome might have been improved by a more gradual introduction of treatment and by use of an eight theophylline from + 1.54 mg/l ± 54%o with initial estimates data indicate that http://thorax.bmj.com/ to + 0.28% mg/l ± 8.6%o with revised estimates. The system hourly dosage schedule, but the has been put onto a Sirius microcomputer and gives theophylline use in this age group needs to be critically re- printouts of predicted concentration-time curves on any evaluated. dosage regime. This has proved very easy to use. accurate, and of great help in the individualisation of treatment and in the education of those concerned with patient care. Use of asthma treatment in general practice CR HORN, GM COCHRANE It has been reported recently that Rapid analysis of plasma theophylline concentrations in the increasing levels of prescribing of antiasthma drugs have clinical setting failed to reduce the death rate from asthma (Keating G et on September 27, 2021 by guest. Protected al. Br Med J 1984;289:348-5 1). This may be due, in part at FM CUSS, JD PALMER, PJ BARNES The therapeutic effect of least, to a failure of patients to actually use their drugs theophyllines can be optimised with the help of plasma appropriately. In a survey of asthma treatment in general levels. While measurement of plasma theophylline is now practice only two thirds of patients said that they took their possible in many hospitals, only in a very few are they drugs as prescribed. Compliance with maintenance immediately available. In the casualty department or treatment was no better with increasingly severe asthma outpatient clinic theophylline prescribing could be made (assessed both objectively or subjectively) but did improve easier by the rapid estimation of levels before the drug is if the asthma disrupted the patient's life. Increasingly given. Recently a technique has become available using complex regimes were associated with a sharp reduction in solid phase immunochemistry and reflectance photometry compliance, in complete contrast to the pattern in patients (Seralyser, Miles Laboratories Ltd), which is portable and attending a hospital clinic (James P et al. Thorax simple enough to be operated outside the laboratory. 1982;37:778). Compliance was better among female Diluted plasma or serum is pipetted onto a reagent strip, patients and tended to be better among younger patients. which is then analysed in the photometer, the result being Compliance with inhalation treatment was related to displayed 80 seconds later. We have used this system to patients' aerosol technique. Failure of symptom relief measure plasma theophylline levels of 50 consecutive associated with poor aerosol technique may have patients attending outpatient clinics. The results obtained encouraged underuse of inhalation therapy. Attention to Thorax: first published as 10.1136/thx.40.3.209 on 1 March 1985. Downloaded from Proceedings of the British Thoracic Society 231 education of patients with encouragement to use drugs Pulmonary disease in Behcet's syndrome appropriately and efficiently may help to reduce asthma morbidity and possibly mortality. J EFTHIMIOU, SG SPIRO Pulmonary disease is rare in Behcet's syndrome, with a reported incidence of less than 5%. The most common clinical presentation is with haemoptysis, usually accompanied by chest radiograph Twenty-four hour ECG monitoring in patients using air opacities, of which 22 cases have been previously reported. driven nebulisers We describe a further five patients, four of whom presented with an "incomplete" form of Behcet's disease, without D VEALE, JJ GILMARTIN, A MURRAY, PC ADAMS, GJ ocular disease. Pulmonary disease was usually GIBSON The use of large doses of bronchodilators accompanied by active disease at other sites, although delivered by air driven nebulisers is causing concern because haemoptysis was occasionally the sole manifestation. The of possible adverse cardiac effects. We have studied 11 patients showed a male predominance of 4:1 and deep vein patients (10 with asthma) whose regular treatment was from thrombosis and thrombophlebitis were common. Two 5 to 17.5 mg salbutamol daily by nebuliser. The patients patients died with massive haemoptysis due to pulmonary were studied at home on their usual drug regime and kept a haemorrhage. Immunopathological evidence suggests that diary card including peak flow recordings. Ages ranged the underlying pathogenesis is a pulmonary vasculitis, from 32 to 71 years and one subject had recognised which may result in arterial and venous thromboses, coronary artery disease. We recorded a two channel 24 hour pulmonary infarction, pulmonary arterial aneurysms, and ECG to assess the effect of therapy on heart rate, ST pulmonary haemorrhage, Corticosteroids were often segment, and rhythm. Before each dose of nebulised initially of value in clearing the haemoptysis and chest salbutamol the patient rested for 20 minutes and used an radiograph opacities, but long term responses were less event marker to indicate the start and end of therapy. The impressive. Cyclophosphamide was effective in controlling 24 hour tapes were analysed in 20 minute blocks, thus further pulmonary exacerbations in one patient. The allowing comparison between the treatment and rest prognosis in this group is poor and this may be due to periods. Heart rate was not significantly increased by delays in diagnosis as well as to the inappropriate use of nebuliser therapy (rest: mean (SD) 93 (14); during 90 (13) anticoagulants. We suggest that pulmonary involvement be beats/min). Five patients had no ectopic beats at any time included as one of the important "minor" criteria for the of Behcet's during the recording and in the other six patients there was diagnosis syndrome. copyright. an average of 15 ventricular ectopics/hour with no increase during or after therapy. Thus we have found no adverse electrocardiographic effects from these doses of nebulised salbutamol in this group of patients. Hypoxia and secondary polycythaemia: their relative effects on mental function in respiratory disease http://thorax.bmj.com/
PR FARROW, DK PILLAI, GJ FANCOURT, JB COOKSON Impaired Double blind trial of ketoconazole in non-invasive mental alertness has been reported with raised packed cell pulmonary aspergillosis volume (PCV) and proposed as one reason for venesection in polycythaemia. We have investigated the relative effect DJ SHALE, JA FAUX, DJ LANE A double blind trial of of hypoxic polycythaemia and hypoxia alone in mental ketoconazole was undertaken in eight patients with allergic function. Psychometry (Gibson's spiral maze, trail making bronchopulmonary aspergillosis (ABPA) and three with test, critical flicker fusion frequency, simple reaction time, mycetoma. Four received placebo and seven ketoconazole and pursuit rotor score) was performed in 13 patients with 400 mg daily for one year. Serum was collected monthly polycythaemia due to respiratory disease (mean Pao2 6.75 on September 27, 2021 by guest. Protected and on completion of the study anti-Aspergillusfumigatus kPa, PCV 0.59), seven patients with hypoxia but no IgG levels were determined by quantitative ELISA (Shale polycythaemia (mean Pao2 8.25 kPa, PCV 0.41), and 28 and Faux. Thorax 1984;39:239). A daily symptom score healthy controls matched for age, sex and social class (mean was recorded by the ABPA patients. No adverse effects PCV 0.45). Test scores were standardised to the mean and were reported by those receiving ketoconazole. IgG levels variance of the control group so that a combined rating were significantly reduced in the ketoconazole group could be calculated for each individual (after the method of (p<0.05, months 3-10 and 12) compared with two Willison et al. Lancet 1980;i:846-8). There were no pretreatment values. The mean reduction in antibody levels significant differences in ratings between the groups with was 42% (SEM 2.2%). In the placebo group IgG levels were polycythaemia (mean (SD) - 8.38 (5.02)) and hypoxia unchanged (mean +-10% (5.3%)). The symptom scores for alone (mean - 7.58 (4.80)) but both were impaired the ABPA subjects having ketoconazole (4) were (p<0.001) by comparison with controls (mean 0 (3.02)). significantly less than in the placebo group. Compared with Weekly venesections in those with polycythaemia reduced the first month of treatment their mean change was mean PCV to 0.44, but psychometric rating did not +0.45% (6.9%) month and +27% (6.5%) month for the significantly change. Impaired mental function in placebo group (3) (p<0.001). Ketoconazole appears to be respiratory polycythaemia is due to hypoxia rather than an effective suppressant of infection in pulmonary raised packed cell volume and is not improved by aspergillosis and deserves further study. venesection. Thorax: first published as 10.1136/thx.40.3.209 on 1 March 1985. Downloaded from 232 Proceedings of the British Thoracic Society Acute effects of corticosteroids in chronic airflow between the two methods of delivery in terms of obstruction breathlessness, extra bronchodilator used, or two-weekly measures of PEFR, spirometric values, or walking distance. RI GOVE, PS BURGE Forty-two patients with chronic airflow Careful assessment is necessary to determine which patients obstruction were entered into a trial to see whether the might benefit from domiciliary nebulisation. acute response to corticosteroids seen in asthmatics also occurred, and whether such a response was more pronounced among corticosteroid responsive patients. All Maximum activity questionnaire for evaluation of patients clinically needed a trial of corticosteroids and none respiratory disability had received any form of corticosteroid within the preceeding six months. All patients received 1 g of HA BOOKER, CFA PANTIN, DP DHILLON, AH DIMOND, JV hydrocortisone intravenously after baseline flow-volume COLLINS The maximum activity questionnaire measures loop had been recorded and recorded their flow-volume the level of activity at which breathlessness causes the loop hourly thereafter for six hours. All patients had subject to stop and rest. Its score S covers no restriction abstained from their usual bronchodilators for the (100%) to complete disability (0%) in daily activities preceeding 12 hours. Two weeks later the patients attempted. On admission to hospital, at discharge, and underwent a double blind placebo controlled trial of 40 mg three weeks after discharge 29 patients with airflow prednisolone daily for two weeks. Fourteen patients limitation were assessed with spirometry, six minute satisfied the criteria of a response on the basis of having a walking distance (6MWD), and the questionnaire and greater than 20% increase in FEVI, FVC, or mean daily graded on a 0-5 disability scale by an independent observer peak flow following prednisolone. Although appreciable (AHD). On admission S (median 70%0, range 5-100%o) increases in expiratory flow occured in some patients correlated with FEV1 (r = 0.46, p<0.02) and 6MWD following hydrocortisone, increases in FEV1, FVC, (median 391 range 120-690 m)(r=0.80, p<0.001). The maximum inspiratory flow, and flow at 50% of the vital percentage of daily activities attempted (median 55%o range capacity were not significantly greater in the corticosteroid 29-89%) correlated with 6MWD (r = 0.41, p<0.05). The responsive group than in the non-responders (for example, scatter of S and 6MWD in each clinical grade was wide, but increase in FEVI, (o) mean ± (SD)): responders 15 (9), means decreased as grades fell from 0 to 5. On follow up non-responders 13 (10)). The acute response to the observer only changed his disability grading in 26/60 hydrocortisone seen in asthmatics, although sometimes possible pairs of assessments; of these 19 were measured by seen in patients with chronic airflow obstruction, does not both S and 6MWD, three by 6MWD alone and four by S copyright. distinguish corticosteroid responders from non-responders. alone. The improvement or deterioration in 6MWD and S agreed in 37 pairs of assessments and disagreed in 10, and in 13 either 6MWD or S were unchanged. We believe that this Comparison of domiciliary salbutamol nebuliser and questionnaire provides a quantitative measure of metered dose inhaler (MDI) in stable chronic airflow respiratory disability and will be of particular benefit in the http://thorax.bmj.com/ limitation assessment of the effects of breathlessness on daily activity.
SC JENKINS, RW HEATON, J MOXHAM Current interest in methods of delivering bronchodilators, and reports from Practical experience of long term prostacyclin in patients patients of greater benefit from nebulisation than from with primary pulmonary hypertension MDI, prompted us to investigate these two forms of inhalation therapy. We studied 15 patients (9M) with K JONES, T HIGENBOTTAM, J WALLWORK We have treated chronic airflow limitation, mean FEVY 0.53 1 (range seven patients with pulmonary hypertension (five presumed 0.35-0.9 1), secondary to chronic bronchitis, emphysema, or primary) with continuous intravenous prostacyclin (PGI2) chronic asthma. The doses of salbutamol inhaled via the at home. Five patients with primary pulmonary on September 27, 2021 by guest. Protected nebuliser and MDI were established by cumulative dose- hypertension are alive and well with treatment. Two response curves for PEFR, FEVI, and VC, the minimum patients have died, one with pulmonary veno-occlusive dose from each system producing greatest response in a disease associated with systemic sclerosis and one with a given patient being used. Patients inhaled double blind presumed vasculitis. Initial studies showed that there was either salbutamol nebuliser and placebo MDI or saline an acute response to 4-6 ng/kg/min of PGI2. The mean nebuliser and salbutamol MDI in an eight week trial with (SD) pulmonary artery pressure fell from 70 (18) to 59 (17) two weekly crossover. Daily PEFR before and after each mm Hg and cardiac output rose from 3.6 (1) to 4.3 (1.2) treatment, breathlessness on a visual analogue scale, and I/min. Pulmonary vascular resistance fell from 16.7 (7) to extra symptomatic usage of bronchodilator were recorded 10.7 (5.5) Wood units. In four patients exercise tested by the patient. Two weekly assessment of PEFR, FEVI, before and after prostacyclin infusion using a mechanical and VC, before and after treatment, and a walking test treadmill there was a rise in maximum oxygen consumption were performed. The dose of salbutamol given via the of 78% (74)01o and horizontal walking speed of 280%o nebuliser was 2.5-5 mg (mode 5 mg) and via the MDI (29807o). In line with improved exercise tolerance, 200-600 ,g (mode 200 pg). For the group mean daily PEFR symptoms also improved. PGI2 was delivered by a before and after treatment was higher with nebulised tunnelled subclavian line and an electric syringe pump. Side salbutamol than with MDI, but this was significant in only effects included the development of ascites in three patients a minority of patients. There was no significant difference and in one the line became unattached at home. Mean Thorax: first published as 10.1136/thx.40.3.209 on 1 March 1985. Downloaded from Proceedings of the British Thoracic Society 233 duration of therapy is 7 (6.5) months. While prolonging Tomographic measurements of regional ventilation- and improving the quality of life, intravenous PG12 can be perfusion and VA/AQ using krypton 81m considered only as a means of "buying time" for more definitive therapy. D. ORPHANIDOU, AR AL-SUHALI, JP LAVENDER, MJ MYERS, JMB HUGHES Krypton 81m (I/2 13 s; n-emission 190 keV) was Bone marrow transplantation: prospective study of lung inhaled and infused intravenously continuously for 12 function minutes while a gamma camera rotated around the thorax giving 64 images of 4 and Q). From these multiple views axial HG KENNEDY, SE WYATr, J APPERLEY, L HOPPER, JM GOLDMAN, tomographic slices of the entire lung were reconstructed. JMB HUGHES Pulmonary complications are common Counts per voxel were plotted for regions of interest causes of morbidity and mortality after bone marrow 1.2 x 1.2 x 0.6 cm3. Ten studies were performed in five transplantation. A prospective study of spirometry, and normal subjects in supine, prone, and R and L lateral carbon monoxide transfer (TLco) by the single breath decubitus postures. Two studies (before and after nebulised method was undertaken. Nine patients transplanted for salbutamol) were done in two asthmatics in the supine chronic granulocytic leukaemia were followed for six posture. In normal subjects ventilation was greater in months. Before transplantation daunorubicin 60 mg/m2, dependent lung regions (upper/lower (U/L) ratos 0.5-0.52) cyclophosamide 60 mg/kg (x2), and total body irradiation except in the prone position (U/L 1.14). Along a horizontal (1 000 cGy in five fractions were given. After axis, independent of gravity, cranial ventilation exceeded transplantation cyclosporin and prednisolone (100 mg x 5) caudal (Cr/Cau ratio 1.1-1.19) except prone (0.73). Lower were given. There was a significant fall in Kco - that is, (dependent) zone perfusion always exceeded upper: U/L TLCO per unit alveolar volume (VA), which progressed ratio 0.73-0.77 (supine/prone) and 0.37-0.38 (R and L during the six months period. The trend for vital capacity lateral). Cranial Q) exceeded caudal (Cr/Cau 1.27-1.32) and alveolar volume by helium dilution (VA) to decline except prone (Cr/Cau 0.87. Lower zone V/4) exceeded upper reached significance at six months. The present regimen for (U/L 1.33-1.48) except supine (U/L 0.68). Cranial 4/Q bone marrow transplantation is damaging to the lungs, and exceeded caudal (0.85-0.91) in all postures. In general research is required to prevent this. perfusion and ventilation follow a pattern dictated by gravity, independent of posture. It is of interest that, MONTHS: 0 1 3 6 independent of gravity, cranial V and Q exceed caudal. There are anomalies in the prone posture which are unexplained. 102 106 96 Abnormal were found in the asthmatic and copyright. Mean VC (18) 99 (14) (1) (15) gradients subjects (SD) KCO 90 (14) 82' (9) 77* (8) 75* (12) changes in regional V, Q, and VA/0 were seen after the bronchodilator. n = 9. Values are ¾o predicted, VA given as % TLC. Two way analysis of variance; *p 0.01, **p Flow rate Mean increase TcPO2 (mm Hg) a-b (il/min) (a) Reservoir (b) Conventional (Wilcoxon's signed rank) Effect of intermittent positive pressure breathing and jet 0.5 8.2 5.6 p'0.05 nebuliser on the breathing pattern 1.0 13.4 9.0 p<0.01 2.0 19.8 17.4 NS GA CHADWICK, K GLAZEBROOK, JR STRADLING, DJ LANE We Thorax: first published as 10.1136/thx.40.3.209 on 1 March 1985. Downloaded from 234 Proceedings of the British Thoracic Society have examined the effect of breathing salbutamol or followed by either salbutamol 10 pg/min or aminophylline placebo via intermittent positive pressure breathing (IPPB) 6 mg/kg over 30 minutes. Minute ventilation was measured or jet nebuliser on breathing pattern and arterial oxygen over the last five minutes of each infusion with a Wright saturation (Sao2) in 10 patients with chronic airways respirometer. The ventilatory response to carbon dioxide by obstruction. Ventilation was measured by inductance the hyperoxic rebreathing method was then determined. plethysmography in a fixed posture, so that breathing Both salbutamol and aminophylline produced a significant during the control was completely unencumbered. increase in minute ventilation (p Vagal influence on the breathing pattern of resting normal subjects Clinical evaluation of a successive rebreathe procedure to measure the ventilatory response to hypoxia AJ WINNING, RD HAMILTON, SA SHEA, A GUZ Airway anaesthesia has previously been shown to have no effect on NN STANLEY This new test has been validated previously in resting ventilation in man (Cross et al. Clin Sci Mol Med healthy subjects (Stanley. Clin Sci 1984;67:4P), but was 1976;50:439-54), though recently this has been disputed conceived for clinical purposes. By using different test copyright. (Savoy et al. Respir Physiol 1982;50:41-9). We have gases, during monitoring of end tidal CO2 tension (PETCO2) examined its effect on the breathing pattern at rest, without and ear 02 saturation (Sao2), effects of progressive use of a mouthpiece, by respiratory inductance asphyxia and hyperoxic hypercapnia on ventilation (4) are plethysmography. Ventilation and its subdivisions were compared to calculate AV/A Sao2 when PETCO2 iS 1.0 kPa measured in five normal men, aged 23-54 years, for five above mixed venous Co2 tension. In 10 unselected patients minutes before and after inhalation of saline and 5%o with severe chronic airflow obstruction, AV/A Sao2 was http://thorax.bmj.com/ bupivacaine aerosols. Analysis of variance was used to lower (0.48 (SEM 0.06) l/min/oSao2) than in six elderly compare the mean values of tidal volume (VT), inspiratory controls (1.44 (0.19) l/min/%SAo2) (p<0.001), but was and expiratory time (TI, TE) for breaths from each subject virtually zero in two selected patients with inappropriate before and after each aerosol. There was no significant alveolar hypoventilation whose 4 was unresponsive to difference between the means for VT (p>0.5), TI (p>0.7), nitrogen inhalation. A4/A Sao2 increased on average by or TE (p>0.6). The degree of variability in Vi, TI, and TE 74%o after administration of a peripheral chemoreceptor was determined from the ratio of the variances of the agonist (almitrine 100 mg orally) to four with chronic samples before and after each aerosol by using an F table. airflow obstruction. Judged by quadruplicate on in The variability in VT was unchanged after saline aerosol but measurements different days four others, the average on September 27, 2021 by guest. Protected was increased (p<0.05) in four subjects after bupivacaine coefficient of variation in AV/A Sao2 was 1907. compared aerosol. Neither aerosol had any consistent effect on the with 2607. in their ventilatory response to progressive variability of TI or TE. A similar finding has been reported hyperoxic hypercapnia. The procedure is usually well with vagal blockade in awake dogs (Kelsen et al. Respir tolerated and provides a practical and non-invasive means Physiol 1982;49:339-53) and suggests that airway receptors of quantifying ventilatory responsiveness to hypoxia, as in man minimise breath by breath fluctuations in VT well as to hypercapnia, in patients with abnormal lungs without affecting its mean level or respiratory timing at when conventional isocapnic tests are inappropriate rest. because maintaining stable PETCO2 does not ensure isocapnia in their chemoreceptors. A comparison of the effect of aminophylline and salbutamol on minute ventilation and the ventilatory Breathlessness caused by hypoxia is not due only to response to carbon-dioxide stimulation of ventilation AH MORICE, PM SCHOFIELD, PS SEVER, EE KEAL In a single AR GELLERT, RM RUDD Recent work has suggested that blind study six normal volunteers, three male, age range breathlessness induced by hypoxaemia is attributable only 24-32 years, were given an intravenous infusion of placebo to stimulation of ventilation (Swinburn et al. Clin Sci Thorax: first published as 10.1136/thx.40.3.209 on 1 March 1985. Downloaded from Proceedings of the British Thoracic Society 235 1984;66:55P). We used almitrine to investigate the apnoea and oxygen desaturation have been reported to hypothesis that hypoxaemia increases breathlessness by a occur frequently in normal, asymptomatic men and mechanism additional to its effect on ventilation. We postmenopausal women (Block AJ. N Engl J Med compared the effects of 100 mg oral almitrine and placebo 1979;300:513-7; Am JMed 1980;69:75-9). We have studied on breathlessness and ventilation during progressive respiration during sleep in normals, 14 men (mean age 46.8 isocapnic hypoxia in 13 normal males, mean age 30.5 years years), 13 premenopausal women (mean age 30.5 years), (range 26-36). Minute ventilation was integrated from a and nine postmenopausal women (mean age 54.6 years). pneumotachograph in a rebreathing circuit, arterial oxygen Airflow was assessed with a laryngeal microphone, chest saturation (Sao2) was estimated by ear oximetry, and and abdominal wall movement with inductance coils, and breathlessness was repeatedly assessed with 10 cm visual haemoglobin oxygen saturation (Sao2) with an ear lobe analogue scales (VAS). The mean increases in ventilation oximeter. Sleep stage was obtained from with decreasing Sao2 was 1.44 1 min-I % saturation-' electroencephalogram, electro-oculogram, and submental (0.67-2.69) after almitrine, significantly greater than 0.72 electromyogram. Five of the men showed episodes of (0.18-1.56) after placebo (p<0.01). The increase in VAS central apnoea (31,30,2,1,1, episodes each), and one of score for breathlessness with increasing ventilation was 2.1 obstructive apnoea (10). None of the men showed Sao2 mm 1-l min-1 (0.8-5.9) after almitrine, significantly less <90% for> 1 minute, mean time for (Sao2 <95% was than 2.6 (1.2-7.6) after placebo (p<0.01). These results short (3.75 min). One postmenopausal woman had two show that for a given level of ventilation induced by short central apnoeas. Sao2 was lower in the hypoxia breathlessness was greater after placebo than after postmenopausal women than the premenopausal (awake almitrine, probably because Sao2 was lower at that level of mean Sao2, postmenopausal v premenopausal, 967o v ventilation after placebo than at the same level of 97.7%, asleep mean Sao2 94.8 v 96.6%, min Sao2 91.8 v ventilation after almitrine. Hence arterial hypoxaemia 94%). Only two subjects had periods with < 90% Sao2 (5 increases breathlessness by a mechanism additional to the min, 2 min each). We conclude that sleep apnoeas do occur increase in breathlessness caused by stimulation of in normal subjects but are not frequent, and that Sao2 ventilation. <90/o is unusual for significant periods in normal subjects. It is not advisable to contrast published normal controls from American series with United Kingdom patients. Changes in ventilation and its components in normal subjects during sleep copyright. GA CHADWICK, JR STRADLING, AJ FREW Ventilation, its subdivisions, the contributions by abdomen and ribcage, Sleep apnoea and hypoventilation in obesity and arterial oxygen saturation have been measured non- invasively in six healthy normal men, awake and during MCP APPS, PG KOPELMAN, PJW WALLIS, T COPE, DW http://thorax.bmj.com/ sleep. The use of inductance plethysmography avoided EMPEY Both nocturnal hypoventilation and sleep apnoea artefacts induced by mouthpieces or masks and yielded have been reported in obese subjects. We have studied information about ribcage and abdominal contributions to respiration during sleep in 21 obese men (>120Kg), 14 ventilation. A fixed posture was maintained in a tilting obese premenopausal women (>100 kg), 10 obese chair. This is necessary to ensure accuracy, a point not postmenopausal women (>100kg), and 6 women with previously appreciated. Minute ventilation fell significantly hypothalamopituitary disease and abdominal wall during slow wave sleep (SWS) and rapid eye movement movement with inductance coils, and haemoglobin oxygen sleep (REMS): awake = 6.28 I/min, SWS = 5.67 I/min, saturation (Sao2) by ear lobe oximeter. Sleep stage was REMS = 5.44 I/min (p<0.04). Mean inspiratory flow rate obtained from electroencephalogram, electro-oculogram, also fell significantly but timing was unchanged. The and submental electro-myogram. Four of the obese men on September 27, 2021 by guest. Protected abdominal (diaphragmatic) contribution to ventilation fell had frequent episodes of obstructive apnoea, (apnoea index very significantly during SWS but returned to awake levels >10 apnoeas/hour), associated with desaturation, loud during REMS: awake=54io, SWS=38%, REMS=56% snoring, frequent waking, and daytime hypersomnolence. (p<0.007). These changes in ribcage and abdominal Four of the men had frequent central apnoeas (apnoea contribution may have important consequences in patients index >10/hour), with desaturation waking, and daytime with compromised diaphragm function. There were also tiredness. None of the premenopausal women showed significant falls in Sao2 during SWS and REMS: apnoeas. Four post-menopausal women showed severe awake=97.3%, SWS=96.5%, REMS=96.2%; nocturnal desaturation, three with a normal respiratory (p<0.002). These falls in Sao2 represent reductions in Pao2 rhythm and hypoventilation, (Sao2 minimum <601o), and similar to those seen in patients with chronic airways one with frequent obstructive apnoeas. In the obstruction and can entirely be accounted for by the hypothalamo-pituitary group two women showed associated reduction in ventilation. obstructive apnoea, and one central apnoeas. Central apnoeas causing desaturation and waking in both obese men and postmenopausal women occur as frequently as Respiration during sleep in normal men and women obstructive apnoeas. Severe hypoventilaiton may occur in the absence of apnoeas and produce severe nocturnal MCP APPS, PJW WALLIS, DA INGRAM, T COPE, DW EMPEY Sleep hypoxia. Thorax: first published as 10.1136/thx.40.3.209 on 1 March 1985. Downloaded from 236 Proceedings of the British Thoracic Society Ventilation and gas exchange during sleep in patients with Observer error in the estimation of anaerobic threshold pulmonary fibrosis CS GARRARD, R DAS The anaerobic threshold (AT) achieved M COFFEY, WT MCNICHOLAS, MX FITZGERALD We performed during progressive exercise has been proposed as one of the overnight sleep studies on nine patients with severe criteria for determining respiratory disability (American restrictive lung disease due to pulmonary fibrosis (mean Thoracic Society. Am Rev Respir Dis 1983;126:945-51). vital capacity 52 ± 13% predicted; diffusing capacity 46 + However, the AT derived from the visual inspection of the 19% predicted) to see if respiratory abnormalities occur plots of ventilation (VE), CO2 production (VCo2), similar to those previously described during sleep in respiratory exchange ratio (R), or the ventilatory equivalent patients with severe chronic obstructive pulmonary disease. for oxygen (VE/Oo2) against the oxygen uptake (Vo2) is Eight patients had no significant airflow obstruction. inevitably associated with observer error. To quantitate this Ventilation during sleep was measured by inductance error we exercised six healthy volunteers six times and plethysmography and oxygen saturation (Sao2) by ear submitted plots of the above ventilation parameters in oximetry. Awake Pao2 for the group was 8.45 ± 2.26 kPa. random order to four independent observers. Three way All patients had episodes of oxygen desaturation during ANOVA of AT values (expressed as Vo2) showed sleep (minimum Sao2 85% (4.7%) versus 94% (4.1%) significant between observer variations (p<0.001) and during wakefulness; p<0.01). However, the mean Sao2 significant variation between the ventilation parameters showed little change in that among seven patients who had (p<0.001). A significant observer-ventilation parameter periods of rapid eye movement (REM) sleep, Sao2 fell from interaction was demonstrated (p<0.00l) due to one 94.6% (0.5%) during wakefulness to 93.3 ± 1.1% during observer consistently overestimating the AT from the R stage II sleep and to only 92.2% (2.3%) during REM sleep. plots. The lowest mean values for AT were obtained with Minute ventilation showed a progressive fall as sleep the VE and VCO2 plots (1.81 and 1.69 I/min Vo2) and the deepened being lowest in REM sleep, where the ribcage highest with R and VE/VO2 plots (2.28 and 2.6 I/min Vo2). contribution to breathing fell significantly. One patient had Observer error for Vt plots = 10/, for VCO2 = 11 %0, for frequent (40) obstructive apnoeas during sleep and another R = 26%, and for Ve/Vo2=10%1o. The magnitude of had a marked Cheyne-Stokes breathing pattern. In these observer error should therefore be taken into consideration patients episodes of greatest desaturation occured during when using AT data in the evaluation of patient disability. apnoeic periods. We conclude that mild oxygen desaturation may occur during sleep in patients with pulmonary fibrosis, but much less so than that previously copyright. described in patients with chronic obstructive lung disease. Use of bronchoscopic single breath tests to predict functional results of lobectomy http://thorax.bmj.com/ PA CORRIS, AH KENDRICK, GJ GIBSON Preoperative perfusion Some observations on TLCO during exercise in normal scanning allows accurate prediction of post subjects and patients with fibrosing alveolitis pneumonectomy function in bronchial carcinoma but is not directly applicable to lobectomy, where estimation may be AH AL-HILLAWI, D CRAMER, DM DENISON It is known that desirable in patients with borderline function. We have the transfer factor for carbon monoxide (TLCo) rises on therefore assessed the predictive value of the single breath exertion and this may reflect spare capacity in the capillary argon-freon technique (Williams et al. Br J Dis Chest bed. This rise is difficult to demonstrate by the standard 1979;73:97-112) during bronchoscopy prior to lobectomy. single breath technique in dyspnoeic patients. We have Comparison of measurements during sampling at the on September 27, 2021 by guest. Protected compared single breath and rebreathing estimates of TLCO mouth and at successive levels within the bronchial tree in 10 normal subjects at several levels of exertion using the allows estimation of an index of lobar blood flow; adequate Bruce protocol. Single breath TLCO rose linearly to 15707o assessment of lobar function proved possible in 29 of 44 (SD 1907o) of resting value at maximum exertion and patients. Review of the records obtained in the other 15 rebEeathing TLCO to 1460o (11Mo). Correlation coefficients patients showed that inability to calculate lobar function between the two methods were 0.89 at rest, and 0.80 at was usually due to variations in the size of the breaths of stage IV. The mean rise of rebreathing TLCO with increase test gas. The fall in FEVy recorded four months post op. in oxygen consumption was 0.046 mmol/min kPa per was significantly correlated with the pre-operative %o predicted 402 maximum and was significantly greater than function of the affected lobe (n = 29, r = 0.77). Comparison that of 10 patients with cryptogenic fibrosing alveolitis, of the post lobectomy FEV1 with pre-operative estimates whose rise was 0.022 (p<0.001, unpaired t-test). The slope obtained as (pre-operative FEVy (100 - o function of of the rise in TLCO on exertion however was a constant affected lobe)) showed close similarity with a residual SD of fraction of the resting value in normal subjects and patients 5.7% predicted FEVY. The single breath argon/freon (0.005 per %o predicted V02 maximum, r = 0.82). This technique can be successfully used at bronchoscopy to finding suggests that, in this group at least, the accessible estimate post lobectomy function in the majority of capillary volume (as judged by TLCO) is behaving in the patients and may have a role in assessment of patients same manner in normal subjects and patients. where FEVY is borderline for lobectomy. Thorax: first published as 10.1136/thx.40.3.209 on 1 March 1985. Downloaded from Proceedings of the British Thoracic Society 237 Effects of packed cell volume reduction on calf blood flow Haemophilus blotyping in respiratory disease in secondary polycythaemia and cor pulmonale GA GOULD, GB RHIND, F AHMAD, MJ CROUGHAN, M PJW WALLIS, MCP APPS, AC NEWLAND, DW EMPEY Packed cell CALDER We wished to evaluate the recently described volume reduction improves walking distance in patients technique of biotyping of Haemophilus species. During with hypoxic lung disease (Wedzicha JA et al. Br Med J 1983, Haemophilus was isolated from 1086 sputum 1983;286:51 1-4), although the mechanisms are unclear. We specimens, comprising 70% Haemophilus influenzae (HI) have investigated the effects of the procedure on calf blood and 30% Haemophilusparainfluenzae (HP) with indentical flow and oxygen transport. Packed cell volume was lowered proportions in general practice (n = 105) and hospital by erythrapheresis from 0.60 (0.02) to 0.51 (0.02) (mean (n = 981) isolates. HP isolates peaked in winter in contrast (SEM)) in eight patients with secondary polycythaemia and to the spring peak of HI. Subcultures in 954 isolates cor pulmonale (FEVy 0.701, Pao2 6.87 kPa, red cell mass revealed ampicillin resistance in 8V/2%V HI and 7% HP 156% predicted). Resting and postocclusion peak isolates. Biotyping was successful in 49% HP and 75% HI hyperaemic flows were assessed by venous occlusion isolates. Casenotes were examined for biotyped hospital plethysmography. Blood viscosity was significantly reduced isolates and details of symptoms, biotype, antibiotic at shear rates 23/s and 230/s (p<0.002). Arterial oxygen sensitivities, sputum cell count and other organisms were content fell by 18% (p<0.00l). Resting calf blood flow was recorded for each clinical episode (443 HI, 131 HP). not improved (2.32 (0.37) v 2.01 (1.26) ml/lOOml/min; NS) Diagnostic groups were chronic bronchitis (n = 201), and resting oxygen transport to the calf fell by 27% asthma (n = 63), bronchial carcinoma (n = 107), (p<0.05). Peak hyperaemic calf blood flow improved bronchiectasis (n = 52), pneumonia (n = 38) and others significantly following haematocrit reduction (14.61 (0.60) (n = 113). Symptoms were similar for all biotypes of HI and v 17.29 (2.05) ml/lOOml/min; p<0.0l). Despite the HP. In chronic bronchitis 35% HI and 37% HP isolates increased blood flow oxygen transport to the calf during occurred without exacerbation. Biotype distribution and peak hyperaemic flow did not change significantly. In proportion of HI to HP was similar for all diagnostic conclusion, improving the rheological properties of the groups, with the commonest biotypes being HI II > HI III blood by erythrapheresis did not increase oxygen transport > HI I > HP II. We conclude that apart from seasonal to the calf at rest or during peak flow. Walking distance variation the clinical characteristics of HI and HP are may increase because enhanced tissue perfusion improves similar and that Haemophilus biotyping has no clinical or oxygen availability within calf muscle even though the epidemiological value in chest disease. amount of oxygen transported to the calf does not rise. copyright. Do phagocytic cells ingest spores of Aspergillusfumigatus? A simple, selective bacteriological medium designed to distinguish Haemophilus Influenzae from Hparainfluenzae http://thorax.bmj.com/ MD ROBERTSON, JA RAEBURN, IP GORMLEY, A In sputum SEATON Variations in host responses to Aspergillus fumigatus may explain why certain individuals especially D ROBERTS, E HIGGS, C PRIOR, P COLE Haemophilus some asthmatics and the immunosuppressed are susceptible influenzae is distinct from H parainfluenzae in its growth to this fungus. The primary defence mechanisms against requirements - the former requiring both "X" (haemin) inhaled spores is thought to be phagocytosis (Schaffner et and "V" (coenzyme) factors, the latter only "V" factor. al. J Clin Invest 1982;69:617-31). However, to our Unfortunately, since most nutrient agar itself contains knowledge no distinction has yet been made between spores small amounts of "X" factor, tests for distinguishing the which are ingested and those attached to the surface of the species using "X" and "V" factor-impregnated discs are phagocytic cell. We have used a combination of Nomarski liable to result in misclassification of H influenzae as H on September 27, 2021 by guest. Protected differential interference contrast optics, bright field parainfluenzae (Turk and May. Haemophilus influenzae: illumination and electron microscopy to examine the its clinical importance. English Universities Press 1967: 11). interaction of pre-opsonised spores of A fumigatus with We have developed a medium reliably distinguishing the phagocytic cells from humans (monocytes and two species, isolated in primary culture from sputum, and polymorphonuclear leukocytes) and mice (resident and relying on modification of our original selective medium thioglycollate-elicited peritoneal macrophages). We found for H influenzae (Roberts and Cole. Lancet 1980;i:796-7). that the majority of spores appeared to be bound to the cell It allows H parainfluenzae to ferment sucrose in the surface rather than fully ingested. This observation points presence of phenol red - resulting in bright yellow to a need for further studies of the fungicidal mechanisms colonies, H influenzae growing as white colonies. Testing a of phagocytes, perhaps similar to those employed in the variety of clinical isolates and reference strains of destruction of hyphae (Diamond et al. J Infect Dis haemophilus has shown good correlation between sucrose 1983;147:474-83), and may also explain why no evidence of fermentation and growth factor requirements. The clinical phagosome-lysosome fusion has been found after importance of distinguishing the two species lies in the 'phagocytosis' of spores by rabbit alveolar macrophages widely held interpretation of H parainfluenzae as non- (Kurup VP. Immunobiol 1984;166:53-61). Such studies pathogenic (Smith et al. Lancet 1976;i:1253-5), so that could shed some light on why infection with A fumigatus misclassification of H influenzae as Hparainfluenzae might can cause differing clinicopathological features in man. lead to withholding treatment of a candidate pathogen. Thorax: first published as 10.1136/thx.40.3.209 on 1 March 1985. Downloaded from 238 Proceedings ofthe British Thoracic Society Characterisation of a cilioinhibitory factor produced by Treatment response of bronchiectatic secretions with three Pseudomonas aeruginosa amoxycillin regimes R WILSON, D ROBERTS, P COLE Pseudomonas aeruginosa HM MORRISON, SL HILL, RA STOCKLEY Purulent sputum produces a factor or factors which slows human ciliary beat from stable bronchiectatic patients usually contains free frequency (CBF) In vitro (Wilson et al. Thorax, in press). elastase (Stockley et al. Thorax 39:414-19) which can Ten clinical isolates were cultured in medium 199 for 18 damage ciliated bronchial epithelium but be removed with hours, centrifuged and the supernatants aspirated and antibiotic therapy. However, the choice and dose used is filtered to give bacteria free preparations. These were added uncertain as patients do not always respond. Therefore we to human nasal ciliated epithelium, obtained by a brushing studied the antibiotic response and relapse rates in 28 such technique, without dilution. The CBF was measured for patients. Seventeen regularly produced purulent sputum four hours by a photometric technique (Rutland and Cole. (P), six mucoid sputum (M), and five fluctuated between Lancet 1980;ii:564). Maximum cilioinhibition mucopurulent and purulent sputum (MP/P). The patients (test/control x 100 at same experimental time point) ranged received 14 days of low dose amoxycillin (LDA) 250 mg and from 97% to 51 /o and dyskinesia and ciliostasis occurred in non-responders progressed to high dose (HDA) (3G twice some areas of the epithelium. Non-mucoid strains were daily for 14 days) or NA (500 mg twice daily nebulised for more actively cilioinhibitory than mucoid strains. There four months). Fourteen of the patients responded to LDA. was no correlation between supernatant cilioinhibitory All M patients cleared with LDA and had prolonged activity and total protease or elastase activity. Abrogation remission. All MP/P patients responded but of cilioinhibition in active supernatants was achieved by macroscopically relapsed within 7.6 (SD 3.2) days. Only 3 incubation with trypsin (98%) and growth of the organism of the P group cleared and all relapsed within seven days. in the presence of a chelating agent (86%). Freeze-dried Ten of the LDA non-responders received HDA and sputum supernatant, dissolved in a small volume of distilled water, cleared in six, with longer remission (mean 12.8 (7.0)). was passed down a sephacryl-200 column and a single However, a decreasing effect was seen during subsequent cilioinhibitory peak obtained at a molecular weight of courses. Two of the remaining four died and the rest about 3000 daltons. This induced immediate ciliostasis responded to NA. Their secretions have remained when undiluted and ciliostasis after 90 minutes on dilution macroscopically clear over several months after the I in 2. cessation of therapy. The results suggest that a higher dosage of antibiotic is usually necessary to clear the secretions of bronchiectatic patients with persistently copyright. purulent secretions and treatment may need to continue longer than is conventionally considered. http://thorax.bmj.com/ Genesis of histamine in sputum: a role for bacteria in the Pulmonary epithelial permeability in bronchiectasis airflow obstruction of acute exacerbations of chronic obstructive airways disease? TB CHAN, J ANDERSON, NM EISER, PJ REES It has been suggested that the deterioration in lung function in patients BD SHEINMAN, JL DEVALIA, RJ DAVIES Recent work has with generalised bronchiectasis, with or without cystic demonstrated the presence of mediators of inflammation fibrosis, is related to chronic colonisation by respiratory such as histamine and SRS-A in the sputum of patients with pathogens, such as Pseudomonas Aeruginosa. The chronic bronchitis (Turnbull LS et al. Lancet 1977;ii: 526). mechanism may be an increase in pulmonary epithelial Using a fluorimetric assay, Bryant and Pui (Clin Allergy permeability. We have investigated lung permeability by 1982; 12:19) demonstrated elevations in histamine content measuring the half time clearance from lung to blood on September 27, 2021 by guest. Protected when sputum from chronic bronchitics was incubated at (T½2LB) of 99mTc labelled DTPA in 13 non-smoking 37°C for 24 hours. Using a new HPLC assay developed in patients with generalised bronchiectasis, five of whom had our laboratory, we have documented a striking exponential cystic fibrosis. The age range was 16-79 years and the range elevation of histamine content of sputum obtained from of FEVy was 20-85qo predicted. Sputum obtained by seven patients with acute exacerbations of chronic bron- prestudy chest physiotherapy revealed significant colonies chitis when incubated at 37°C for 72 hours. Large rises of Pseudomonas aeruginosa in five, Haemophilus occurred for every patient which were virtually abolished influenzae in three, and Staphylococcus aureus in two by preheating samples at 100°C. For unheated samples patients, while in the remainder there was normal flora mean (SEM) histamine levels increased from 42.9 (23) only. TV/2LB ranged from 20 to 34 minutes in patients with ng/ml on day 0 to 2123 (448) ng/ml on day 3. Differences significant bacterial colonisation of sputum and 42 to 55 between histamine levels in unheated and heated samples minutes in those whose sputum contained only normal were highly significant at 24, 48, and 72 hours (p<0.025, flora. There was no correlation between TA/2LB and pre- p<0.005, and p<0.005 respectively). These results suggest study FEVI. In conclusion, significant colonisation with that bacteria synthesise histamine in sputum. Simultaneous bacterial pathogens in generalised bronchiectasis is measurement of 1-methyl histamine revealed no increase associated with increased pulmonary epithelial in this major histamine metabolite suggesting that no his- permeability. However, this was not associated with worse tamine breakdown occurred. lung function, in the small group studied. Thorax: first published as 10.1136/thx.40.3.209 on 1 March 1985. Downloaded from Proceedings ofthe British Thoracic Society 239 Is cell density a determinant of bronchoalveolar clearance? been described in hay fever sufferers. Histamine induced suppressor cell function was assessed in 12 non-atopic R AGIUS, I PETRICEVIE, R KNIGHT, P COLE The cytology of subjects and 28 hay fever sufferers. An index of sputum or of secretions aspirated from the larger airways is suppression, expressed as a percentage, was derived from remarkably different from that of cells obtained by the ability of lymphocytes stimulated by 0.1 mmol/l bronchoalveolar lavage (BAL), yet little is known about histamine to inhibit concanavalin A induced lymphocyte factors which determine the clearance of the latter cells. transformation. There was no significant difference in the Cells recovered by BAL of 27 patients were centrifuged on mean (SD) suppressor index between non-atopics 15% continuous density gradients of colloidal silica. In 25 cases (16%) and hay fever sufferers 14.5% (18%). Hay fever at least two reproducible bands were evident with mean sufferers underwent nasal challenge with purified Timothy (SEM) densities of 1.027 (0.006) g/ml and 1.041 (0.001) grass pollen to determine the concentration of pollen g/ml respectively. The heavier band contained most of the causing a 100% increase in nasal airway resistance. Patients macrophages (differential 91 070 (4%)) and the cells responding to 1000 biological units of pollen had a possessed trypan blue viability of 89% (2%) which was significantly lower mean suppresor index - 9.8%7 (14%) significantly higher than that in the lighter band (51% (n = 18) - than patients sensitive to 10 000 and 100 000 (3%); p<0.001), and within it macrophage morphology biological units of pollen - 24% (20%) (n = 10: p = 0.025). and cytochemical features were similar to those observed in Our findings suggest that nasal sensitivity in hay fever samples of sputum. These observations prompt the sufferers may be inversely related to suppressor cell hypothesis that cell density, or some factor closely function. associated with it, determines which intraluminal bronchoalveolar cells are preferentially cleared by the mucociliary mechanism. Angiotensin converting enzyme and septic acute respiratory distress syndrome in the mouse The effect of chronic denervation on mucociliary transport WOCM COOKSON, M WISEMAN, DJ SHALE Septic acute in vivo respiratory distress syndrome (SARDS) may be modelled by intraperitoneal injection of Escherichia coli endotoxin in M GREENSTONE, P STANLEY, I MACKAY, P COLE Mucociliary the mouse. Serum Angiotensin converting enzyme (ACE) transport (MCT) in the respiratory tract has been reported falls in SARDS in mice and in humans and has been copyright. to be enhanced by adrenergic and cholinergic agents and proposed as a specific indicator of lung microvascular delayed by their respective antagonists. The effect of insufficiency (Hollinger AM. Am Rev Respir Dis denervation is a model for investigating the contribution of 1983;127:756-7). Serum (S), lung (L), and bronchoalveolar autonomic influences on basal MCT. Acute denervation lavage fluid (BAL) protein concentration (P) and ACE impaired MCT in dogs In vivo (Edmunds et al. Surgery activity were determined in male mice up to eight hours 1969;66:15) but was normal in patients with chronic after injection of endotoxin. By six hours S-P had increased http://thorax.bmj.com/ autonomic failure (Jenkins et al. Thorax 1980;35:690). The (p<0.05), L-P was unaltered, and BAL-P had fallen effect of chronic denervation of nasal mucosa on MCT was (p<0.01), but by eight hours were recovered. S-ACE and studied in seven patients who had previously undergone L-ACE both fell (p<0.001) and p<0.02), whereas BAL- bilateral vidian neurectomy for intractable vasomotor ACE increased (p<0.02), before returning to normal. The rhinitis a mean of 9.7 years (range 4-15) previously. All changes in P were consistent with protein-poor fluid shift patients had evidence of persistent vidian denervation as into the lung, validating this model of SARDS. Although evidenced by impairment of lachrymation. Nasal ACE has a higher molecular weight than P (mostly mucociliary clearance (NMCC) was measured by the albumin), changes in ACE were not paralleled by changes saccharin test. Results were compared with those in a in P, and are not a result of fluid shift or protein leak. control group of 34 non-operated vasomotor rhinitis Active metabolism of ACE by the lung is a more likely on September 27, 2021 by guest. Protected sufferers. Mean NMCC of the vidian neurectomy patients explanation of these results than microvascular failure, and was 15.4 minutes (range 8-28) and was not significantly may represent part of volume and blood pressure different from the vasomotor rhinitis group (mean 19.7 homeostasis after septic insult, rather than simply marking minutes, range 7-50). This suggests that, with time, the lung damage. mucociliary apparatus compensates for interruption of its nerve supply and can achieve normal MCT in the absence of autonomic innervation. Preservation of selective permeability at the capillary- alveolar barrier in adult respiratory distress syndrome Nasal sensitivity and suppressor cell function in hay fever DJ SHAW, H CHAPEL, A HUSSAIN. A FISHER, G de J sufferers LEE Previous studies of proteins in alveolar oedema fluid (Katz et al. Am Rev Respir Dis 1972;106:472) and AG FENNERTY, KP JONES, BH DAVIES An underlying bronchoalveolar lavage fluid (BALF) (Fowler et al. Am Rev abnormality in suppressor T cell function may be Respir Dis 1981;123:S247; Holter et al. Am Rev Respir Dis responsible for the zverproductien- of- IgE in - atepic 1984; 129:Al 1) have suggested a non-selective change in subjects. Suppressor cells can be stimulated by incubating permeability to plasma proteins. Cell types and proteins them with histamine, and a reduction in this response Iar- were det7ermined in plasma and BALF from nine patients Thorax: first published as 10.1136/thx.40.3.209 on 1 March 1985. Downloaded from 240 Proceedings of the British Thoracic Society with adult respiratory distress syndrome (ARDS). of TBA reactive products compared to CV at 10, 15 and 20 Comparison was made with nine patients with interstitial minutes following AoXC removal. These data suggest that lung disease (ILO) and 18 control patients (C). The total any oxidant lung injury associated with cardiopulmonary cell count was reduced in the BALF of ARDS patients bypass may occur during the period of partial bypass. (0.19 x l09/l v 0.58 x 109/l (ILD) v 0.42 x 109/l (C)) and the cell type ratios altered significantly in favour of neutrophils (4301 (ARDS) v 107 (ILD) v 1%7o (C)). Protein content was significantly greater in the ARDS BALF. The ratio BALF: serum was significantly greater in ARDS patients for albumin, transferrin, ceruloplasmin, and C3 component of Complement activation and the change in lung function complement. The relationship of log BALF/serum to with intravenous radiological contrast material molecular weight was linear (y= -0.0077, x + 1.945; r= -0.9751; p<0.05), indicating preservation of molecular N ASHFORD, N CRACKNELL, J MCCARTY, P DOYLE, T selectivity during increased permeability at the capillary HIGENBOTTAM Reactions to intravenous radiological alveolar barrier. contrast material include dyspnoea and wheeze. The mechanism for contrast reactions remains unknown, although in vitro studies suggest activation of complement Neutrophil kinetics and oxidative injury associated with with the generation of C3a (Dawson P. Br J Radiol cardiopulmonary bypass 1983;56:447-8). We have studied 10 patients including 5 smokers undergoing urography using diatrizoate D ROYSTON, JS FLEMING, S WESTABY, J DESAI, K TAYLOR In (Urografin 325). Spirometry was recorded before and five this study we have investigated the time course of egress of minutes after the injection. Lung epithelial permeability neutrophils into the lung in seven patients having surgery was also measured using a small radiolabelled molecule for coronary artery bypass grafting. In addition we 99mTc DTPA as an index of damage to the alveolar measured peroxidation products in the plasma using the capillary barrier (Jones JG. Br J Anaesth 1982;54:705). Thiobarbituric acid (TBA) reaction. This assay was used to Blood samples were taken before and five and 20 minutes give an index of tissue injury induced by oxidant species after injection. Haemoglobin, white cell count and platelet (Fleming JS Artif Organs 1984;8:91-6). Samples of central count were determined together with complement, C3, C4, venous (CV) and left atrial (LA) blood were taken after CH50, and C3a by radioimmunossay (Hugli JE. In: Future administration of heparin (300 U/kg) and at 30 minutes in prospectives in clinical laboratory immunoassays 1980). Nocopyright. bypass and then two minutes prior to and at 5 minute patient suffered any contrast reaction. There was a small intervals up to 25 minutes after removal of the aortic cross but significant fall in FEV1 after contrast injection from, clamp (AoXC) while still on bypass. Samples were analysed FEVY 3.8 to 3.5 1 (t= 3.42; df -9; p<0.01). There was also for white cell, neutrophil and lymphocyte count and plasma a fall in DTPA T½V2, from 28.9 to 21.5 (t=2.55, df=9; TBA reactive products. The results showed that there were p<0.025), indicating increased clearance. However, there no significant differences between CV and LA cell counts were no significant changes in white blood cell or platelet http://thorax.bmj.com/ whilst the AoXC was in place. However, there was a highly counts nor in complement level. Intravenous injection of significant (p<0.001) egress of neutrophils into the lung diatrizoate can cause increased clearance of DTPA and a following AoXC removal. This was associated with a highly reduction in FEVY. Complement activation does not appear significant (p<0.001) rise in CV neutrophil count. There to be the cause, but we suspect direct toxic damage by was also a significantly (p<0.01) higher LA concentration Urografin to the alveolar capillary barrier. Notice on September 27, 2021 by guest. Protected British Thoracic Society: future meetings 3-5 July 1985 University of York, York 11-12 December 1985 Kensington Town Hall, London 18-20 June 1986 Cheltenham Town Hall, Cheltenham Members should note the change of date and venue for the 1985 winter meeting. Abstracts for the summer meeting, July 1985 should be received at the head office, 107 Syd- ney Street, Brompton, London SW3 6NP, by 6 April 1985.